Mutation of a U2 snRNA Gene Causes Global Disruption of Alternative Splicing and Neurodegeneration
Open accessAbstract
Although uridine-rich small nuclear RNAs (U-snRNAs) are essential for pre-mRNA splicing, little is known regarding their function in the regulation of alternative splicing or of the biological consequences of their dysfunction in mammals. Here, we demonstrate that mutation of Rnu2-8, one of the mouse multicopy U2 snRNA genes, causes ataxia and neurodegeneration. Coincident with the observed pathology, the level of mutant U2 RNAs was highest in the cerebellum and increased after granule neuron maturation. Furthermore, neuron loss was strongly dependent on the dosage of mutant and wild-type snRNA genes. Comprehensive transcriptome analysis identified a group of alternative splicing events, including the splicing of small introns, which were disrupted in the mutant cerebellum. Our results suggest that the expression of mammalian U2 snRNA genes, previously presumed to be ubiquitous, is spatially and temporally regulated, and dysfunction of a single U2 snRNA causes neuron degeneration through distortion of pre-mRNA splicing.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mutation of Rnu2-8 leads to specific neurodegeneration in the cerebellum.
“mutation of Rnu2–8, which encodes part of a core spliceosomal component, the U2 small nuclear RNA (snRNA), leads to specific neurodegeneration in the cerebellum.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [182]
NMF291 mice develop tremors at 8 weeks, progressing to truncal ataxia by 12 weeks.
“and develop tremors at 8 weeks, progressing to truncal ataxia by 12 weeks.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [182]
NMF291 mice show progressive and severe degeneration of the cerebellum as a result of the loss of cerebellar granule neurons beginning at postnatal week 4.
“NMF291 mice show progressive and severe degeneration of the cerebellum as a result of the loss of cerebellar granule neurons beginning at postnatal week 4”
From The neurogenetics of alternative splicing (2016) · cites this paper as [182]
The NMF291 mutation is a 5nt deletion that removes the first 2nt of the branch site recognition sequence within the U2 snRNA, as well as a 3nt linker between the branch site recognition sequence and the U2/U6 helix IA.
“The NMF291 mutation is a 5nt deletion that removes the first 2nt of the branch site recognition sequence within the U2 snRNA, as well as a 3nt linker between the branch site recognition sequence and the U2/U6 helix IA.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [182]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · see citing works
Mapping and quantifying mammalian transcriptomes by RNA-Seq
Mortazavi, A., Williams, B. A., McCue, K., Schaeffer, L., & Wold, B. (2008) · Nature Methods · doi:10.1038/nmeth.1226 · Cited by 13,696 · see citing works
Alternative isoform regulation in human tissue transcriptomes
Wang, E. T., Sandberg, R., Luo, S., Khrebtukova, I., Zhang, L., Mayr, C., Kingsmore, S. F., Schroth, G. P., & Burge, C. B. (2008) · Nature · doi:10.1038/nature07509 · Cited by 5,181 · see citing works
Identification and characterization of a spinal muscular atrophy-determining gene
Lefebvre, S., Bürglen, L., Reboullet, S., Clermont, O., Burlet, P., Viollet, L., Bénichou, B., Cruaud, C., Millasseau, P., Zeviani, M., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90460-3 · Cited by 3,995 · see citing works
Mechanisms of Alternative Pre-Messenger RNA Splicing
Black, D. L. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161720 · Cited by 2,704 · see citing works
The Spliceosome: Design Principles of a Dynamic RNP Machine
Wahl, M. C., Will, C. L., & Lührmann, R. (2009) · Cell · doi:10.1016/j.cell.2009.02.009 · Cited by 2,665 · see citing works
Long pre-mRNA depletion and RNA missplicing contribute to neuronal vulnerability from loss of TDP-43
Polymenidou, M., Lagier-Tourenne, C., Hutt, K. R., Huelga, S. C., Moran, J., Liang, T. Y., Ling, S.-C., Sun, E., Wancewicz, E., Mazur, C., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2779 · Cited by 1,335 · see citing works
Characterizing the RNA targets and position-dependent splicing regulation by TDP-43
Tollervey, J. R., Curk, T., Rogelj, B., Briese, M., Cereda, M., Kayikci, M., König, J., Hortobágyi, T., Nishimura, A. L., Župunski, V., et al. (2011) · Nature Neuroscience · doi:10.1038/nn.2778 · Cited by 1,165 · see citing works
Cooper, T. A., Wan, L., & Dreyfuss, G. (2009) · Cell · doi:10.1016/j.cell.2009.02.011 · Cited by 1,160 · see citing works
Exon Recognition in Vertebrate Splicing
Berget, S. M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.6.2411 · Cited by 1,090 · see citing works
TDP-43 and FUS/TLS: emerging roles in RNA processing and neurodegeneration
Lagier-Tourenne, C., Polymenidou, M., & Cleveland, D. W. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq137 · Cited by 1,021 · see citing works
Lerner, E. A., Lerner, M. R., Janeway, C. A., & STEITZ, J. A. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.5.2737 · Cited by 718 · see citing works
Zhang, Z., Lotti, F., Dittmar, K. A., Younis, I., Wan, L., Kasim, M., & Dreyfuss, G. (2008) · Cell · doi:10.1016/j.cell.2008.03.031 · Cited by 610 · see citing works
Ni, J. Z., Grate, L. R., Donohue, J. P., Preston, C. G., Nobida, N., O’Brien, G. S., Shiue, L., Clark, T. A., Blume, J. E., & Ares, M. (2007) · Genes & Development · doi:10.1101/gad.1525507 · Cited by 551 · see citing works
Wollerton, M., Gooding, C., Wagner, E. J., García-Blanco, M. A., & Smith, C. W. J. (2004) · Molecular Cell · doi:10.1016/s1097-2765(03)00502-1 · Cited by 409 · see citing works
A computational analysis of sequence features involved in recognition of short introns
Lim, L. P., & Burge, C. B. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.201407298 · Cited by 376 · see citing works
The EJC Factor eIF4AIII Modulates Synaptic Strength and Neuronal Protein Expression
Giorgi, C., Yeo, G. W.-M., Stone, M. E., Katz, D. B., Burge, C. B., Turrigiano, G. G., & Moore, M. J. (2007) · Cell · doi:10.1016/j.cell.2007.05.028 · Cited by 332 · see citing works
Detection of splice junctions from paired-end RNA-seq data by SpliceMap
Au, K. F., Jiang, H., Lin, L., Xing, Y., & Wong, W. H. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq211 · Cited by 328 · see citing works
RNA toxicity is a component of ataxin-3 degeneration in Drosophila
Li, L.-B., Yu, Z., Teng, X., & Bonini, N. M. (2008) · Nature · doi:10.1038/nature06909 · Cited by 316 · see citing works
Gabanella, F., Butchbach, M. E. R., Saieva, L., Carissimi, C., Burghes, A. H. M., & Pellizzoni, L. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000921 · Cited by 315 · see citing works
Identification of alternative splicing regulators by RNA interference in Drosophila
Park, J. W., Parisky, K. M., Celotto, A. M., Reenan, R. A., & Graveley, B. R. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407004101 · Cited by 290 · see citing works
Discovery of tissue-specific exons using comprehensive human exon microarrays
Clark, T. A., Schweitzer, A. C., Chen, T. X., Staples, M. K., Lu, G., Wang, H., Williams, A., & Blume, J. E. (2007) · Genome biology · doi:10.1186/gb-2007-8-4-r64 · Cited by 280 · see citing works
He, H., Liyanarachchi, S., Akagi, K., Nagy, R. S., Li, J., Dietrich, R. C., Li, W., Sebastian, N., Wen, B., Xin, B., et al. (2011) · Science · doi:10.1126/science.1200587 · Cited by 262 · see citing works
Splicing Regulation in Neurologic Disease
Licatalosi, D. D., & Darnell, R. B. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.017 · Cited by 250 · see citing works
Association of TALS Developmental Disorder with Defect in Minor Splicing Component U4atac snRNA
Edery, P., Marcaillou, C., Sahbatou, M., Labalme, A., Chastang, J., Touraine, R. L., Tubacher, E., Senni, F., Bober, M. B., Nampoothiri, S., et al. (2011) · Science · doi:10.1126/science.1202205 · Cited by 228 · see citing works
Small Nuclear RNA Genes: a Model System to Study Fundamental Mechanisms of Transcription
Hernandez, N. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.r100032200 · Cited by 217 · see citing works
Zhao, L., Longo-Guess, C. M., Harris, B. S., Lee, J.-W., & Ackerman, S. L. (2005) · Nature Genetics · doi:10.1038/ng1620 · Cited by 214 · see citing works
Self-citationRegulation of alternative splicing by the core spliceosomal machineryPreprint
Saltzman, A. L., Pan, Q., & Blencowe, B. J. (2011) · Genes & Development · doi:10.1101/gad.2004811 · Cited by 204 · see citing works
Sequence features responsible for intron retention in human
Sakabe, N. J., & de Souza, S. (2007) · BMC Genomics · doi:10.1186/1471-2164-8-59 · Cited by 164 · see citing works
Nonsense-Mediated RNA Decay Regulation by Cellular Stress: Implications for Tumorigenesis
Gardner, L. B. (2010) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-09-0502 · Cited by 155 · see citing works
Human U1 Loci: Genes for human U1 RNA have dramatically similar genomic environments
Manser, T., & Gesteland, R. F. (1982) · Cell · doi:10.1016/0092-8674(82)90110-6 · Cited by 138 · see citing works
Differential expression of multiple U1 small nuclear RNAs in oocytes and embryos of Xenopus laevis
Forbes, D. J., Kirschner, M. W., Caput, D., Dahlberg, J. E., & Lund, E. (1984) · Cell · doi:10.1016/0092-8674(84)90263-0 · Cited by 128 · see citing works
Splicing factor and exon profiling across human tissues
de la Grange, P., Gratadou, L., Delord, M., Dutertre, M., & Auboeuf, D. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq008 · Cited by 127 · see citing works
Pre-mRNA splicing and retinitis pigmentosa.
Mordes, D. A., Luo, X., Kar, A. N., Kuo, D. C., Xu, L., Fushimi, K., Yu, G., Sternberg, P., & Wu, J. Y. (2006) · PubMed · Cited by 121 · see citing works
Human genes for U2 small nuclear RNA are tandemly repeated.
Arsdell, S. W. V., & Weiner, A. M. (1984) · Molecular and Cellular Biology · doi:10.1128/mcb.4.3.492 · Cited by 119 · see citing works
Differential Control of U1 Small Nuclear RNA Expression During Mouse Development
Lund, E., Kahan, B. W., & Dahlberg, J. E. (1985) · Science · doi:10.1126/science.2412294 · Cited by 116 · see citing works
Expression of human snRNA genes from beginning to end
Egloff, S., O’Reilly, D., & Murphy, S. (2008) · Biochemical Society Transactions · doi:10.1042/bst0360590 · Cited by 110 · see citing works
Evolution of Spliceosomal snRNA Genes in Metazoan Animals
Marz, M., Kirsten, T., & Stadler, P. F. (2008) · Journal of Molecular Evolution · doi:10.1007/s00239-008-9149-6 · Cited by 97 · see citing works
FAST DB: a website resource for the study of the expression regulation of human gene products
de la Grange, P. (2005) · Nucleic Acids Research · doi:10.1093/nar/gki738 · Cited by 95 · see citing works
Analysis of Eukaryotic mRNA Structures Directing Cotranslational Incorporation of Selenocysteine
Kollmus, H., Flohé, L., & McCarthy, J. E. G. (1996) · Nucleic Acids Research · doi:10.1093/nar/24.7.1195 · Cited by 89 · see citing works
de la Grange, P., Dutertre, M., Correa, M., & Auboeuf, D. (2007) · BMC Bioinformatics · doi:10.1186/1471-2105-8-180 · Cited by 78 · see citing works
RNA metabolism and the pathogenesis of motor neuron diseases
Lemmens, R., Moore, M. J., Al‐Chalabi, A., Brown, R. H., & Robberecht, W. (2010) · Trends in Neurosciences · doi:10.1016/j.tins.2010.02.003 · Cited by 77 · see citing works
Pavelitz, T., Rusché, L. N., Matera, A. G., Scharf, J. M., & Weiner, A. M. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb06987.x · Cited by 77 · see citing works
Clustered genes for human U2 RNA.
Westin, G., Zabielski, J., Hammarström, K., Monstein, H., Bark, C., & Pettersson, U. (1984) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.81.12.3811 · Cited by 70 · see citing works
Sauterer, R. A., Feeney, R. J., & Zieve, G. W. (1988) · Experimental Cell Research · doi:10.1016/0014-4827(88)90336-9 · Cited by 69 · see citing works
Corioni, M., Antih, N., Tanačković, G., Zavolan, M., & Krämer, A. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq1042 · Cited by 62 · see citing works
An Analysis on Gene Architecture in Human and Mouse Genomes
Sakharkar, M. K., Perumal, B. S., Sakharkar, K. R., & Kangueane, P. (2005) · In Silico Biology · doi:10.3233/isb-00192 · Cited by 60 · see citing works
Human Genes for U2 Small Nuclear RNA Are Tandemly Repeated
Arsdell, S. W. V., & Weiner, A. M. (1984) · Molecular and Cellular Biology · doi:10.1128/mcb.4.3.492-499.1984 · Cited by 55 · see citing works
Smith, D. J., Konarska, M. M., & Query, C. C. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.03.012 · Cited by 43 · see citing works
Nasim, T. (2002) · Nucleic Acids Research · doi:10.1093/nar/gnf108 · Cited by 42 · see citing works
The abundance of the spliceosomal snRNPs is not limiting the splicing of U12-type introns
Pessa, H. K. J., Ruokolainen, A., & Frilander, M. J. (2006) · RNA · doi:10.1261/rna.213906 · Cited by 38 · see citing works
Chacko, E., & Ranganathan, S. (2009) · BMC Genomics · doi:10.1186/1471-2164-10-s1-s5 · Cited by 37 · see citing works
Deletion of the N-terminus of SF2/ASF Permits RS-Domain-Independent Pre-mRNA Splicing
Shaw, S. D., Chakrabarti, S., Ghosh, G., & Krainer, A. R. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000854 · Cited by 28 · see citing works
The silk moth Bombyx mori U1 and U2 snRNA variants are differentially expressed
Sierra-Montes, J. M., Pereira‐Simon, S., Smail, S. S., & Herrera, R. J. (2005) · Gene · doi:10.1016/j.gene.2005.02.013 · Cited by 27 · see citing works
The conserved central domain of yeast U6 snRNA: Importance of U2-U6 helix Ia in spliceosome assembly
Ryan, D. E., & Abelson, J. N. (2002) · RNA · doi:10.1017/s1355838202025013 · Cited by 26 · see citing works
Mutation in the U2 snRNA influences exon interactions of U5 snRNA loop 1 during pre‐mRNA splicing
McGrail, J. C., Tatum, E. M., & O’Keefe, R. T. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601258 · Cited by 25 · see citing works
Isolation and characterization of developmentally regulated sea urchin U2 snRNA genes
Stefanovic, B., Li, J.-M., Sakallah, S. A., & Marzluff, W. F. (1991) · Developmental Biology · doi:10.1016/0012-1606(91)90337-3 · Cited by 16 · see citing works
Zahler, A. M., Tuttle, J. D., & Chisholm, A. D. (2004) · Genetics · doi:10.1534/genetics.104.028746 · Cited by 16 · see citing works
A genome end-game: understanding gene function in the nervous system
Bult, C. J., Kibbe, W. A., Snoddy, J. R., Vitaterna, M. H., Swanson, D. J., Pretel, S., Li, Y., Hohman, M. M., Rinchik, E. M., Takahashi, J. S., et al. (2004) · Nature Neuroscience · doi:10.1038/nn0504-484 · Cited by 11 · see citing works
Mutagenesis of Mouse Embryonic Stem Cells with Ethylmethanesulfonate
Munroe, R., & Schimenti, J. C. (2009) · Methods in molecular biology · doi:10.1007/978-1-59745-471-1_7 · Cited by 11 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The neurogenetics of alternative splicing
Vuong, C. K., Black, D. L., & Zheng, S. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.27 · Cited by 340 · see citing works
Genome-wide discovery of human splicing branchpointsPreprint
Mercer, T. R., Clark, M. B., Andersen, S. B., Brunck, M. E. G., Haerty, W., Crawford, J., Taft, R. J., Nielsen, L. K., Dinger, M. E., & Mattick, J. S. (2015) · Genome Research · doi:10.1101/gr.182899.114 · Cited by 244 · see citing works
Wang, E., & Aifantis, I. (2020) · Trends in cancer · doi:10.1016/j.trecan.2020.04.011 · Cited by 242 · see citing works
Hsieh, Y.-C., Guo, C., Yalamanchili, H. K., Abreha, M., Al-Ouran, R., Li, Y., Dammer, E. B., Lah, J. J., Levey, A. I., Bennett, D. A., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.104 · Cited by 196 · see citing works
Yan, K., Liu, P., Wu, C., Yang, G., Xu, R., Guo, Q., Huang, J., & Zheng, C. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.08.032 · Cited by 190 · see citing works
RNA 2′-O-Methylation (Nm) Modification in Human Diseases
Dimitrova, D. G., Teysset, L., & Carré, C. (2019) · Genes · doi:10.3390/genes10020117 · Cited by 187 · see citing works
RNA components of the spliceosome regulate tissue- and cancer-specific alternative splicingPreprint
Dvinge, H., Guenthoer, J., Porter, P. L., & Bradley, R. K. (2019) · Genome Research · doi:10.1101/gr.246678.118 · Cited by 143 · see citing works
Watson, C. N., Belli, A., & Pietro, V. D. (2019) · Frontiers in Genetics · doi:10.3389/fgene.2019.00364 · Cited by 148 · see citing works
Jangi, M., Fleet, C., Cullen, P. F., Gupta, S. V., Mekhoubad, S., Chiao, E. T., Allaire, N., Bennett, C. F., Rigo, F., Krainer, A. R., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1613181114 · Cited by 130 · see citing works
Spatially exploring RNA biology in archival formalin-fixed paraffin-embedded tissues
Bai, Z., Zhang, D., Gao, Y. P., Tao, B., Zhang, D., Bao, S., Enninful, A., Wang, Y., Li, H., Su, G., et al. (2024) · Cell · doi:10.1016/j.cell.2024.09.001 · Cited by 118 · see citing works
Human mutations in integrator complex subunits link transcriptome integrity to brain development
Oegema, R., Baillat, D., Schot, R., van Unen, L., Brooks, A., Kia, S. K., Hoogeboom, A. J. M., Xia, Z., Li, W., Cesaroni, M., et al. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006809 · Cited by 108 · see citing works
Regulation of alternative mRNA splicing: old players and new perspectives
Dvinge, H. (2018) · FEBS Letters · doi:10.1002/1873-3468.13119 · Cited by 105 · see citing works
Differentially expressed, variant U1 snRNAs regulate gene expression in human cellsPreprint
O’Reilly, D., Dienstbier, M., Cowley, S. A., Vazquez, P., Drożdż, M., Taylor, S., James, W., & Murphy, S. (2012) · Genome Research · doi:10.1101/gr.142968.112 · Cited by 99 · see citing works
Lardelli, R. M., Schaffer, A. E., Eggens, V. R., Zaki, M. S., Grainger, S. J., Sathe, S., Nostrand, E. L. V., Schlachetzki, Z., Rosti, B., Akizu, N., et al. (2017) · Nature Genetics · doi:10.1038/ng.3762 · Cited by 97 · see citing works
Mutation in noncoding RNA RNU12 causes early onset cerebellar ataxia
Elsaid, M. F., Chalhoub, N., Ben‐Omran, T., Kumar, P., Kamel, H., Ibrahim, K. O., Mohamoud, Y. A., Al‐Dous, E., Al-Azwani, I. K., Malek, J. A., et al. (2016) · Annals of Neurology · doi:10.1002/ana.24826 · Cited by 93 · see citing works
Lei, L., Yan, S., Yang, R., Chen, J., Li, Y., Bu, Y., Chang, N., Zhou, Q., Zhu, X., Li, C., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw1043 · Cited by 85 · see citing works
Non-coding RNAs and disease: the classical ncRNAs make a comeback
de Almeida, R. A., Fraczek, M. G., Parker, S., Delneri, D., & O’Keefe, R. T. (2016) · Biochemical Society Transactions · doi:10.1042/bst20160089 · Cited by 83 · see citing works
Non-Coding RNAs in Psychiatric Disorders and Suicidal Behavior
Yoshino, Y., & Dwivedi, Y. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.543893 · Cited by 82 · see citing works
Genomic variations in non-coding RNAs: Structure, function and regulation
Bhartiya, D., & Scaria, V. (2016) · Genomics · doi:10.1016/j.ygeno.2016.01.005 · Cited by 72 · see citing works
The regulation and function of post-transcriptional RNA splicing
Choquet, K., Patop, I. L., & Churchman, L. S. (2025) · Nature Reviews Genetics · doi:10.1038/s41576-025-00836-z · Cited by 71 · see citing works
PARIS: Psoralen Analysis of RNA Interactions and Structures with High Throughput and Resolution
Lu, Z., Gong, J., & Zhang, Q. C. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7213-5_4 · Cited by 67 · see citing works
Sleigh, J. N., Barreiro‐Iglesias, A., Oliver, P. L., Biba, A., Becker, T., Davies, K. E., Becker, C. G., & Talbot, K. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt477 · Cited by 66 · see citing works
Non-Coding RNAs in Human Cancer and Other Diseases: Overview of the Diagnostic Potential
Beňačka, R., Szabóová, D., Guľašová, Z., Hertelyová, Z., & Radoňak, J. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242216213 · Cited by 65 · see citing works
Regulation of Toll-like Receptor Signaling by the SF3a mRNA Splicing Complex
O’Connor, B. P., Danhorn, T., Arras, L. D., Flatley, B. R., Marcus, R. A., Farias‐Hesson, E., Leach, S. M., & Alper, S. (2015) · PLoS Genetics · doi:10.1371/journal.pgen.1004932 · Cited by 62 · see citing works
Chen, P., Han, X., Shaw, T. I., Fu, Y., Sun, H., Niu, M., Wang, Z., Jiao, Y., Teubner, B. J. W., Eddins, D. M., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00290-0 · Cited by 60 · see citing works
Greene, D., Wispelaere, K. D., Lees, J. G., Codina‐Solà, M., Jensson, B. Ö., Hales, E., Katrinecz, A., Molina, E. N., Pascoal, S., Pfundt, R., et al. (2025) · Nature Genetics · doi:10.1038/s41588-025-02159-5 · Cited by 60 · see citing works
Karri, V., Ramos, D., Bauzá‐Martinez, J., Odena, M. A., de Oliveira, E., Coort, S. L., Evelo, C. T., Mariman, E. C. M., Schuhmacher, M., & Kumar, V. (2018) · Journal of Proteomics · doi:10.1016/j.jprot.2018.06.020 · Cited by 63 · see citing works
Kargapolova, Y., Levin, M., Lackner, K. J., & Danckwardt, S. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx152 · Cited by 55 · see citing works
Loss of function mutations in GEMIN5 cause a neurodevelopmental disorder
Kour, S., Rajan, D. S., Fortuna, T. R., Anderson, E. N., Ward, C., Lee, Y., Lee, S., Shin, Y. B., Chae, J., Choi, M., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22627-w · Cited by 54 · see citing works
Human spliceosomal snRNA sequence variants generate variant spliceosomes
Mabin, J. W., Lewis, P. W., Brow, D. A., & Dvinge, H. (2021) · RNA · doi:10.1261/rna.078768.121 · Cited by 46 · see citing works
Functional and genetic analysis of choroid plexus development in zebrafish
Henson, H. E., Parupalli, C., Ju, B., & Taylor, M. R. (2014) · Frontiers in Neuroscience · doi:10.3389/fnins.2014.00364 · Cited by 44 · see citing works
Li, S., Pan, Z., Chen, L., Dai, Y., Wan, J., Ye, H., Nguyen, H. T., Zhang, G., & Chen, H. (2020) · Genes · doi:10.3390/genes11121520 · Cited by 48 · see citing works
Linder, B., Hirmer, A., Gal, A., Rüther, K., Bolz, H. J., Winkler, C., Laggerbauer, B., & Fischer, U. (2014) · PLoS ONE · doi:10.1371/journal.pone.0111754 · Cited by 45 · see citing works
Biochemical defects in minor spliceosome function in the developmental disorder MOPD I
Jafarifar, F., Dietrich, R. C., Hiznay, J. M., & Padgett, R. A. (2014) · RNA · doi:10.1261/rna.045187.114 · Cited by 44 · see citing works
Post-transcriptional regulation of myotube elongation and myogenesis by Hoi Polloi
Johnson, A. N., Mokalled, M. H., Valera, J. M., Poss, K. D., & Olson, E. N. (2013) · Development · doi:10.1242/dev.095596 · Cited by 46 · see citing works
Karri, V., Schuhmacher, M., & Kumar, V. (2020) · Food and Chemical Toxicology · doi:10.1016/j.fct.2020.111257 · Cited by 44 · see citing works
Alternative splicing interference by xenobiotics
Zaharieva, E. E., Chipman, J. K., & Soller, M. (2012) · Toxicology · doi:10.1016/j.tox.2012.01.014 · Cited by 43 · see citing works
Tissue plasminogen activator regulates Purkinje neuron development and survival
Li, J., Yu, L., Gu, X., Ma, Y., Pasqualini, R., Arap, W., Snyder, E. Y., & Sidman, R. L. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1305010110 · Cited by 43 · see citing works
Developmental Analysis of Spliceosomal snRNA Isoform Expression
Lu, Z., & Matera, A. G. (2014) · G3 Genes Genomes Genetics · doi:10.1534/g3.114.015735 · Cited by 40 · see citing works
Choquet, K., Baxter‐Koenigs, A. R., Dülk, S.-L., Smalec, B. M., Rouskin, S., & Churchman, L. S. (2023) · Nature Structural & Molecular Biology · doi:10.1038/s41594-023-01035-2 · Cited by 39 · see citing works
Insights into the U1 small nuclear ribonucleoprotein complex superfamily
Guiro, J., & O’Reilly, D. (2014) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1257 · Cited by 38 · see citing works
Vazquez‐Arango, P., Vowles, J., Browne, C., Hartfield, E. M., Fernandes, H. J. R., Mandefro, B., Sareen, D., James, W., Wade‐Martins, R., Cowley, S. A., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw711 · Cited by 37 · see citing works
Sin, O., & Nollen, E. A. A. (2015) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-015-1985-0 · Cited by 37 · see citing works
Laurent, G. S., Savva, Y. A., & Kapranov, P. (2012) · Frontiers in Genetics · doi:10.3389/fgene.2012.00057 · Cited by 35 · see citing works
Competition between maturation and degradation drives human snRNA 3′ end quality controlPreprint
Lardelli, R. M., & Lykke‐Andersen, J. (2020) · Genes & Development · doi:10.1101/gad.336891.120 · Cited by 36 · see citing works
Cerebellar ataxia and functional genomics: Identifying the routes to cerebellar neurodegeneration
Smeets, C. J. L. M., & Verbeek, D. S. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.04.004 · Cited by 34 · see citing works
Interaction of 7SK with the Smn complex modulates snRNP production
Ji, C., Bader, J. M., Ramanathan, P., Hennlein, L., Meissner, F., Jablonka, S., Mann, M., Fischer, U., Sendtner, M., & Briese, M. (2021) · Nature Communications · doi:10.1038/s41467-021-21529-1 · Cited by 33 · see citing works
Gem Depletion: Amyotrophic Lateral Sclerosis and Spinal Muscular Atrophy Crossover
Cauchi, R. J. (2014) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12242 · Cited by 31 · see citing works
Kwak, Y. D., Shaw, T. I., Downing, S. M., Tewari, A., Jin, H., Li, Y., Dumitrache, L. C., Katyal, S., Khodakhah, K., Russell, H. R., et al. (2021) · Science Advances · doi:10.1126/sciadv.abg6363 · Cited by 30 · see citing works
BRAT1 links Integrator and defective RNA processing with neurodegeneration
Cihlářová, Z., Kubovčiak, J., Sobol, M. A., Krejčíková, K., Šáchová, J., Kolář, M., Staněk, D., Bařinka, C., Yoon, G., Caldecott, K. W., et al. (2022) · Nature Communications · doi:10.1038/s41467-022-32763-6 · Cited by 30 · see citing works
Maffioli, E., Schulte, C., Nonnis, S., Scalvini, F. G., Piazzoni, C., Lenardi, C., Negri, A. L., Milani, P., & Tedeschi, G. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00417 · Cited by 29 · see citing works
Defective structural RNA processing in relapsing-remitting multiple sclerosis
Spurlock, C. F., Tossberg, J. T., Guo, Y. P., Sriram, S., Crooke, P. S., & Aune, T. M. (2015) · Genome biology · doi:10.1186/s13059-015-0629-x · Cited by 28 · see citing works
U1 snRNP Alteration and Neuronal Cell Cycle Reentry in Alzheimer Disease
Bai, B. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00075 · Cited by 27 · see citing works
Role of Ser7 phosphorylation of the CTD during transcription of snRNA genes
Egloff, S. (2012) · RNA Biology · doi:10.4161/rna.21166 · Cited by 27 · see citing works
Jo, S. H., Park, H. J., Lee, A., Jung, H., Park, J. M., Kwon, S., Kim, H., Lee, H., Kim, Y., Jung, C., et al. (2022) · The Plant Cell · doi:10.1093/plcell/koac084 · Cited by 25 · see citing works
CPEB3 regulates neuron-specific alternative splicing and involves neurogenesis gene expression
Qu, W., Jin, H., Chen, B., Liu, J., Li, R., Guo, W., & Tian, H. (2020) · Aging · doi:10.18632/aging.202259 · Cited by 23 · see citing works
Variant snRNPs: New players within the spliceosome system
Vazquez‐Arango, P., & O’Reilly, D. (2017) · RNA Biology · doi:10.1080/15476286.2017.1373238 · Cited by 23 · see citing works
Banday, A. R., Baumgartner, M., Seesi, S. A., Karunakaran, D. K. P., Venkatesh, A., Congdon, S., Lemoine, C., Kilcollins, A. M., Măndoiu, I., Punzo, C., et al. (2014) · Cell Cycle · doi:10.4161/15384101.2015.941757 · Cited by 22 · see citing works
U1 snRNA over-expression affects neural oscillations and short-term memory deficits in mice
Kumari, E., Shang, Y., Cheng, Z., & Zhang, T. (2019) · Cognitive Neurodynamics · doi:10.1007/s11571-019-09528-x · Cited by 21 · see citing works
Functional Interplay between Small Non-Coding RNAs and RNA Modification in the Brain
Leighton, L. J., & Bredy, T. W. (2018) · Non-Coding RNA · doi:10.3390/ncrna4020015 · Cited by 20 · see citing works
Chen, T., Zhang, B., Ziegenhals, T., Prusty, A. B., Fröhler, S., Grimm, C., Hu, Y., Schaefke, B., Fang, L., Zhang, M., et al. (2019) · PLoS Genetics · doi:10.1371/journal.pgen.1008460 · Cited by 20 · see citing works
Direct Visualization of the Highly Polymorphic RNU2 Locus in Proximity to the BRCA1 Gene
Tessereau, C., Buisson, M., Monnet, N., Imbert, M., Barjhoux, L., Schluth‐Bolard, C., Sanlaville, D., Conseiller, E., Ceppi, M., Sinilnikova, O. M., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076054 · Cited by 19 · see citing works
Sperm-borne sncRNAs: potential biomarkers for semen fertility?
Sellem, E., Jammes, H., & Schibler, L. (2021) · Reproduction Fertility and Development · doi:10.1071/rd21276 · Cited by 18 · see citing works
Brazane, M., Dimitrova, D. G., Pigeon, J., Paolantoni, C., Ye, T., Marchand, V., Silva, B. D., Schaefer, É., Angelova, M. T., Stark, Z., et al. (2023) · Life Science Alliance · doi:10.26508/lsa.202201877 · Cited by 17 · see citing works
USP15 Deubiquitinates TUT1 Associated with RNA Metabolism and Maintains Cerebellar Homeostasis
Kim, J., Nakamura, J., Hamada, C., Taketomi, T., Yano, S., Okajima, T., Kashiwabara, S., Baba, T., Sato, B., Chiba, T., et al. (2020) · Molecular and Cellular Biology · doi:10.1128/mcb.00098-20 · Cited by 17 · see citing works
Abramczuk, M. K., Burkard, T. R., Rolland, V., Steinmann, V., Duchek, P., Jiang, Y., Wissel, S., Reichert, H., & Knoblich, J. A. (2017) · Development · doi:10.1242/dev.152199 · Cited by 16 · see citing works
Wang, C., Ge, Y., Li, R., He, G., & Lin, Y. (2023) · Gene · doi:10.1016/j.gene.2023.147250 · Cited by 16 · see citing works
Transcriptome programs involved in the development and structure of the cerebellum
Farini, D., Marazziti, D., Geloso, M. C., & Sette, C. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03911-w · Cited by 16 · see citing works
The detection, function, and therapeutic potential of RNA 2'-O-methylation
Wu, K., Li, Y., Yang, Y., Yu, Y., Wang, Y., Zhang, L., Cao, Q., & Chen, K. (2024) · The Innovation Life · doi:10.59717/j.xinn-life.2024.100112 · Cited by 12 · see citing works
Fujita, K., Ishizuka, T., Mitsukawa, M., Kurata, M., & Masuda, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21062026 · Cited by 12 · see citing works
Chen, H., Li, N., Xu, Y., Li, G., Song, C., Yao, R., Yu, T., Wang, J., & Yang, L. (2021) · Neurogenetics · doi:10.1007/s10048-021-00675-0 · Cited by 12 · see citing works
Frost, F. G., Morimoto, M., Sharma, P., Ruaud, L., Belnap, N., Calame, D. G., Uchiyama, Y., Matsumoto, N., Oud, M. M., Ferreira, E. A., et al. (2023) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2023.03.001 · Cited by 13 · see citing works
Kosmyna, B., Gupta, V., & Query, C. C. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.01.24.917260 · Cited by 10 · see citing works
Chen, L., Roake, C. M., Maccallini, P., Bavasso, F., Dehghannasiri, R., Santonicola, P., Mendoza-Ferreira, N., Scatolini, L., Rizzuti, L., Esposito, A., et al. (2022) · Nucleic Acids Research · doi:10.1093/nar/gkac659 · Cited by 10 · see citing works
Role of LEDGF/p75 (PSIP1) in oncogenesis. Insights in molecular mechanism and therapeutic potential
Akele, M. Z., Iervolino, M., Belle, S. V., Christ, F., & Debyser, Z. (2024) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2024.189248 · Cited by 9 · see citing works
Onodera, O., Ishihara, T., Shiga, A., Ariizumi, Y., Yokoseki, A., & Nishizawa, M. (2013) · Neuropathology · doi:10.1111/neup.12070 · Cited by 9 · see citing works
Harnessing deep learning into hidden mutations of neurological disorders for therapeutic challenges
Yang, S., Kim, S.-H., Kang, M., & Joo, J. (2023) · Archives of Pharmacal Research · doi:10.1007/s12272-023-01450-5 · Cited by 8 · see citing works
Meng, D., Zheng, Q. S., Zhang, X., Piao, X., Luo, L., & Jia, Y. (2022) · Protein & Cell · doi:10.1093/procel/pwac008 · Cited by 7 · see citing works
Self-citationSmall nuclear RNA genes in Mendelian disorders
Antonarakis, S. E. (2025) · Nature Genetics · doi:10.1038/s41588-025-02440-7 · Cited by 7 · see citing works
A sart1 Zebrafish Mutant Results in Developmental Defects in the Central Nervous System
Henson, H. E., & Taylor, M. R. (2020) · Cells · doi:10.3390/cells9112340 · Cited by 6 · see citing works
Li, G., Xu, D., Huang, G., Bi, Q., Yang, M., Shen, H., & Liu, H. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.885651 · Cited by 6 · see citing works
A Mycobacterium tuberculosis secreted virulence factor Rv1435c/hsr1 disrupts host snRNP biogenesis
Chauhan, K. N. K., Datta, D., Kapoor, Y., Passricha, N., Dutt, R., Arora, N., Das, M., Rao, K., Singh, L., Gautam, A., et al. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2423349122 · Cited by 5 · see citing works
Wang, M., Liang, A.-M., Zhou, Z., Pang, T.-L., Fan, Y., & Xu, Y. (2023) · PLoS Genetics · doi:10.1371/journal.pgen.1011021 · Cited by 4 · see citing works
Anwar, D., Takahashi, H., Watanabe, M., Suzuki, M., Fukuda, S., & Hatakeyama, S. (2016) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2016.06.001 · Cited by 4 · see citing works
van der Stijl, R., Withoff, S., & Verbeek, D. S. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2017.08.003 · Cited by 4 · see citing works
Zhou, S., Lizarazo, S., Chorghade, S., Mouli, L., Cheng, R., Rajendra, K. C., Kalsotra, A., & Bortle, K. V. (2025) · Nature Communications · doi:10.1038/s41467-025-65448-x · Cited by 3 · see citing works
Oshiquiri, L. H., Gomes, S. L., & Georg, R. D. C. (2020) · Fungal Biology · doi:10.1016/j.funbio.2020.03.008 · Cited by 3 · see citing works
My road to alternative splicing control: from simple paths to loops and interconnections
Chabot, B. (2015) · Biochemistry and Cell Biology · doi:10.1139/bcb-2014-0161 · Cited by 3 · see citing works
Nguyen, H. D., Das, U., & Xie, J. (2019) · RNA Biology · doi:10.1080/15476286.2019.1697548 · Cited by 3 · see citing works
Zhu, W., Wei, X., Wang, Y., Li, J., Lü, P., Zhang, K., & Bai, B. (2020) · ACS Omega · doi:10.1021/acsomega.0c03568 · Cited by 3 · see citing works
Dual-targeting snRNA gene therapy rescues STMN2 and UNC13A splicing in TDP-43 proteinopathiesPreprint
Gomberg, T. A., Elmsaouri, S., Kopalle, H., Baughn, M. W., Beccari, M. S., McAlonis‐Downes, M., Artates, J. W., Pant, D., Mak, H., Smargon, A. A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.01.691001 · Cited by 3 · see citing works
Epitranscriptome‐Mediated Regulation of Neuronal Translation
Qadri, S. W., Shah, N. M., & Muddashetty, R. S. (2025) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.70004 · Cited by 2 · see citing works
Chen, L., Roake, C. M., Maccallini, P., Bavasso, F., Dehghannasiri, R., Santonicola, P., Mendoza-Ferreira, N., Scatolini, L., Rizzuti, L., Esposito, A., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.10.27.356782 · Cited by 2 · see citing works
Tsao, W., Huang, Y.-C., Sung, H.-H., Lin, C., Hsu, H., Lin, H., & Chien, C. (2025) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-025-05860-0 · Cited by 1 · see citing works
Crespin, M., Siquier-Pernet, K., Marzin, P., Bôle‐Feysot, C., Malan, V., Nitschké, P., Hully, M., Roux, C., Lemoine, M., Rio, M., et al. (2024) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2024.100372 · Cited by 1 · see citing works
Li, T., Zeng, F., Li, Y., Li, H., & Wu, J. (2024) · Functional & Integrative Genomics · doi:10.1007/s10142-024-01479-9 · Cited by 1 · see citing works
m RNA Splicing: Role of sn RNA s
Padgett, R. A. (2015) · Wiley eBooks · doi:10.1002/9780470015902.a0000879.pub3 · Cited by 1 · see citing works
Functional and Genetic Analysis of Choroid Plexus Development in Zebrafish
Henson, H. E. (2014) · doi:10.21007/etd.cghs.2014.0134 · Cited by 1 · see citing works
A Mycobacterium tuberculosis secreted virulence factor disrupts host snRNP biogenesisPreprint
Chauhan, K. N. K., Passricha, N., Kapoor, Y., Datta, D., Arora, N., Das, M., Rao, K., Singh, L., Dutt, R., Sharma, R. D., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.02.06.579120 · Cited by 1 · see citing works
- Authors
- Jia, Y., Mu, J. C., & Ackerman, S. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- Stanford University (US)
- Corresponding author
- Ackerman, Susan L.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 148
- Issue
- 1-2
- Pages
- 296-308
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3488875
- OpenAlex
- W2114706544
- Cited by
- 114
- References
- 59
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 8 · 2023: 7 · 2022: 6 · 2021: 8 · 2020: 13 · 2019: 7 · 2018: 5 · 2017: 8 · 2016: 7 · 2015: 8 · 2014: 9 · 2013: 5 · 2012: 7
- FWCI
- 3.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 563 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- National Institutes of Health (R01HG004634, R01HG005717)
- National Cancer Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- U2 small nuclear RNA, alternative splicing, neurodegeneration, ataxia, cerebellum, granule neurons, pre-mRNA splicing, gene expression profiling, mouse mutations
- MeSH terms
- Animals, Ataxia, Base Sequence, Cerebellum, Molecular Sequence Data, Mutation, RNA, Small Nuclear, Mutagenesis, Sequence Alignment, Alternative Splicing, Neurodegenerative Diseases, Gene Expression Profiling, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
