Neuronal Elav-like (Hu) proteins regulate RNA splicing and abundance to control glutamate levels and neuronal excitability
Open accessAbstract
The paraneoplastic neurologic disorders target several families of neuron-specific RNA binding proteins (RNABPs), revealing that there are unique aspects of gene expression regulation in the mammalian brain. Here, we used HITS-CLIP to determine robust binding sites targeted by the neuronal Elav-like (nElavl) RNABPs. Surprisingly, nElav protein binds preferentially to GU-rich sequences in vivo and in vitro, with secondary binding to AU-rich sequences. nElavl null mice were used to validate the consequence of these binding events in the brain, demonstrating that they bind intronic sequences in a position dependent manner to regulate alternative splicing and to 3'UTR sequences to regulate mRNA levels. These controls converge on the glutamate synthesis pathway in neurons; nElavl proteins are required to maintain neurotransmitter glutamate levels, and the lack of nElavl leads to spontaneous epileptic seizure activity. The genome-wide analysis of nElavl targets reveals that one function of neuron-specific RNABPs is to control excitation-inhibition balance in the brain.
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ELAVL4 regulates glutamate levels and neuronal excitability.
“glutamate levels, and neuronal excitability (Ince-Dunn et al., 2012; Jung and Lee, 2021)”
From ELAVL4, splicing, and glutamatergic dysfunction precede neuron loss in MAPT mutation cerebral organoids (2021) · cites this paper as Ince-Dunn et al., 2012
The Results section, “A new role for nElavl in regulating glutamate in the brain” (page not provided), reports reduced glutamate in mice lacking both Elavl3 and Elavl4. The Results section, “Seizures in Elavl3-/- Mice” (page not provided), links abnormal cortical activity to loss of Elavl3. These findings support a role for the neuronal Elav-like proteins collectively, but do not establish that ELAVL4 alone regulates both glutamate levels and neuronal excitability. (LLM, conf=0.86)
Experimental — accuracy not yet measurednELAVs preferentially bind introns surrounding cassette exons, especially near exon/intron splice junctions.
“The same report also used genome wide analysis to map the binding sites in nELAV targeted pre-mRNAs and revealed that these proteins preferentially bind introns surrounding cassette exons, especially near exon/intron splice junctions (Ince-Dunn et al. 2012).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Ince-Dunn et al. 2012
nELAVs generate a longer Gls mRNA variant, indicating that they may enhance inclusion of a Gls 3′ exon(s).
“In addition, a recent report identified intronic nELAV binding sites flanking an alternative 3′ SS in the Gls1/Gls gene and demonstrated that nELAVs generate a longer Gls mRNA variant, indicating that they may enhance inclusion of a Gls 3′ exon(s) (Ince-Dunn et al. 2012).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Ince-Dunn et al. 2012
nELAVs enhance exon inclusion when bound to 5′ splice sites in the downstream intron and inhibit exon inclusion when bound to adjacent 3′ and 5′ splice sites of alternative exons.
“In line with previous studies, nELAVs were found to enhance exon inclusion when bound to 5′ SSs in the downstream intron and inhibit exon inclusion when bound to adjacent 3′ and 5′ SSs of alternative exons.”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Ince-Dunn et al. 2012
FMRP is a seminal example of an ASD-associated RNA-binding protein; other ASD-associated RBPs include CELF4, ELAVL3, and GIGYF1.
“A seminal example is the Fragile X mental retardation protein (FMRP) (Darnell et al., 2011), and other RBPs that are associated with ASD include CELF4 (Wagnon et al., 2012), ELAVL3 (Ince-Dunn et al., 2012) and GIGYF1 (Peter et al., 2017).”
From Getting to the cores of autism (2019) · cites this paper as Ince-Dunn et al., 2012
The regulatory programmes of nuclear and cytoplasmic nELAVL proteins are distinct.
“Interestingly, the biological processes affected at the level of splicing are different from those affected at the level of transcript abundance, suggesting that the regulatory programmes of the nuclear and cytoplasmic nELAVL proteins are distinct118.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [118]
ELAVL proteins recognize U- and AU-rich elements.
“that recognize U- and AU-rich elements112–118”
From The neurogenetics of alternative splicing (2016) · cites this paper as [118]
ELAVL3 is the only nELAVL protein in Purkinje cells.
“The specificity of the motor defect may be because ELAVL3 is the only nELAVL protein in Purkinje cells118.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [118]
The biological processes affected at the level of splicing are different from those affected at the level of transcript abundance for nELAVLs.
“Interestingly, the biological processes affected at the level of splicing are different from those affected at the level of transcript abundance, suggesting that the regulatory programmes of the nuclear and cytoplasmic nELAVL proteins are distinct118.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [118]
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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
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkn923 · Cited by 14,108 · 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
Fitting a mixture model by expectation maximization to discover motifs in biopolymers.
Bailey, T. L., & Elkan, C. (1994) · PubMed · Cited by 4,933 · see citing works
Pan, Q., Shai, O., Lee, L. J., Frey, B. J., & Blencowe, B. J. (2008) · Nature Genetics · doi:10.1038/ng.259 · Cited by 3,951 · see citing works
FMRP Stalls Ribosomal Translocation on mRNAs Linked to Synaptic Function and Autism
Darnell, J. C., Van Driesche, S. J., Zhang, C., Hung, K. Y. S., Mele, A., Fraser, C. E., Stone, E. F., Chen, C., Fak, J. J., Chi, S. W., et al. (2011) · Cell · doi:10.1016/j.cell.2011.06.013 · Cited by 2,072 · see citing works
Self-citationHITS-CLIP yields genome-wide insights into brain alternative RNA processing
Licatalosi, D. D., Mele, A., Fak, J. J., Ule, J., Kayikci, M., Chi, S. W., Clark, T. A., Schweitzer, A. C., Blume, J. E., Wang, X., et al. (2008) · Nature · doi:10.1038/nature07488 · Cited by 1,352 · cited 16× · see citing works
“…it does so in clusters, analogous to the way in which Nova proteins recognize specific targets by binding clusters of low complexity YCAY elements (Licatalosi et al., 2008; Zhang et al., 2010). nElav Regulation of Alternative Splicing Previous studies in Drosophila have indicated that nElavl…”
InfluentialSelf-citationCharacterizing 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
Self-citationiCLIP reveals the function of hnRNP particles in splicing at individual nucleotide resolution
König, J., Zarnack, K., Rot, G., Curk, T., Kayikci, M., Zupan, B., Turner, D. J., Luscombe, N. M., & Ule, J. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1838 · Cited by 1,126 · see citing works
Self-citationCLIP Identifies Nova-Regulated RNA Networks in the Brain
Ule, J., Jensen, K. B., Ruggiu, M., Mele, A., Ule, A., & Darnell, R. B. (2003) · Science · doi:10.1126/science.1090095 · Cited by 1,120 · see citing works
Self-citationBrennan, C. M., & Steitz*, J. A. (2001) · Cellular and Molecular Life Sciences · doi:10.1007/pl00000854 · Cited by 1,095 · see citing works
Barash, Y., Calarco, J. A., Gao, W., Pan, Q., Wang, X., Ofer Shai, A., Blencowe, B. J., & Frey, B. J. (2010) · Nature · doi:10.1038/nature09000 · Cited by 891 · see citing works
RNA processing and its regulation: global insights into biological networks
Licatalosi, D. D., & Darnell, R. B. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2673 · Cited by 760 · see citing works
Self-citationTranscriptome-wide Analysis of Regulatory Interactions of the RNA-Binding Protein HuR
Lebedeva, S., Jens, M., Theil, K., Schwanhäusser, B., Selbach, M., Landthaler, M., & Rajewsky, N. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.06.008 · Cited by 716 · see citing works
Mukherjee, N., Corcoran, D. L., Nusbaum, J. D., Reid, D. W., Georgiev, S., Hafner, M., Ascano, M., Tuschl, T., Ohler, U., & Keene, J. D. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.06.007 · Cited by 654 · see citing works
Regulation of γ‐Aminobutyric Acid Synthesis in the Brain
Martin, D. L., & Rimvall, K. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03165.x · Cited by 615 · see citing works
CLIP: A method for identifying protein–RNA interaction sites in living cells
Ule, J., Jensen, K. B., Mele, A., & Darnell, R. B. (2005) · Methods · doi:10.1016/j.ymeth.2005.07.018 · Cited by 597 · see citing works
Self-citationDiverse molecular functions of Hu proteins
Hinman, M. N., & Lou, H. (2008) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-008-8252-6 · Cited by 587 · see citing works
McBain, C. J., & Fisahn, A. (2001) · Nature Reviews Neuroscience · doi:10.1038/35049047 · Cited by 581 · see citing works
Yeo, G. W., Coufal, N. G., Liang, T. Y., Peng, G. E., Fu, X.-D., & Gage, F. H. (2009) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1545 · Cited by 572 · see citing works
Szabo, A., Dalmau, J., Manley, G., Rosenfeld, M., Wong, E., Henson, J., Posner, J. B., & Furneaux, H. M. (1991) · Cell · doi:10.1016/0092-8674(91)90184-z · Cited by 553 · see citing works
An RNA map predicting Nova-dependent splicing regulation
Ule, J., Stefani, G., Mele, A., Ruggiu, M., Wang, X., Taneri, B., Gaasterland, T., Blencowe, B. J., & Darnell, R. B. (2006) · Nature · doi:10.1038/nature05304 · Cited by 528 · see citing works
Self-citationGenome-Wide Identification of Human RNA Editing Sites by Parallel DNA Capturing and Sequencing
Li, J. B., Levanon, E. Y., Yoon, J.-K., Aach, J., Xie, B., LeProust, E. M., Zhang, K., Gao, Y., & Church, G. M. (2009) · Science · doi:10.1126/science.1170995 · Cited by 525 · see citing works
Nova regulates brain-specific splicing to shape the synapse
Ule, J., Ule, A., Spencer, J., Williams, A., Hu, J.-S., Cline, M., Wang, H., Clark, T., Fraser, C., Ruggiu, M., et al. (2005) · Nature Genetics · doi:10.1038/ng1610 · Cited by 509 · see citing works
Self-citationIdentification of a target RNA motif for RNA-binding protein HuR
de Silanes, I. L., Zhan, M., Lal, A., Yang, X., & Gorospe, M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0306453101 · Cited by 502 · see citing works
Astrocytic control of glutamatergic activity: astrocytes as stars of the show
Hertz, L., & Zielke, H. R. (2004) · Trends in Neurosciences · doi:10.1016/j.tins.2004.10.008 · Cited by 470 · see citing works
Xue, Y., Zhou, Y., Wu, T., Zhu, T., Ji, X., Kwon, Y.-S., Zhang, C., Yeo, G., Black, D. L., Sun, H., et al. (2009) · Molecular Cell · doi:10.1016/j.molcel.2009.12.003 · Cited by 469 · see citing works
Self-citationHITS-CLIP: panoramic views of protein-RNA regulation in living cells
Darnell, R. B. (2010) · WIREs RNA · doi:10.1002/wrna.31 · Cited by 382 · see citing works
Self-citationA Hierarchy of Hu RNA Binding Proteins in Developing and Adult Neurons
Okano, H. J., & Darnell, R. B. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-09-03024.1997 · Cited by 379 · see citing works
Self-citationNeuronal regulation of alternative pre-mRNA splicing
Li, Q., Lee, J.-A., & Black, D. L. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2237 · Cited by 376 · see citing works
Castle, J. C., Zhang, C., Shah, J. K., Kulkarni, A., Kalsotra, A., Cooper, T. A., & Johnson, J. M. (2008) · Nature Genetics · doi:10.1038/ng.264 · Cited by 319 · see citing works
Self-citationDefining the regulatory network of the tissue-specific splicing factors Fox-1 and Fox-2
Zhang, C., Zhang, Z., Castle, J., Sun, S., Johnson, J., Krainer, A. R., & Zhang, M. Q. (2008) · Genes & Development · doi:10.1101/gad.1703108 · Cited by 300 · see citing works
Self-citationT HE B IOLOGY OF E PILEPSY G ENES
Noebels, J. L. (2003) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.26.010302.081210 · Cited by 296 · see citing works
Self-citationIntegrative Modeling Defines the Nova Splicing-Regulatory Network and Its Combinatorial Controls
Zhang, C., Frias, M. A., Mele, A., Ruggiu, M., Eom, T., Marney, C. B., Wang, H., Licatalosi, D. D., Fak, J. J., & Darnell, R. B. (2010) · Science · doi:10.1126/science.1191150 · Cited by 294 · see citing works
Self-citationLlorian, M., Schwartz, S., Clark, T. A., Hollander, D., Tan, L.-Y., Spellman, R., Gordon, A., Schweitzer, A. C., de la Grange, P., Ast, G., et al. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1881 · Cited by 263 · see citing works
The Neuronal RNA Binding Protein Nova-1 Recognizes Specific RNA Targets In Vitro and In Vivo
Buckanovich, R. J., & Darnell, R. B. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.6.3194 · Cited by 259 · see citing works
Self-citationiCLIP Predicts the Dual Splicing Effects of TIA-RNA Interactions
Wang, Z., Kayikci, M., Briese, M., Zarnack, K., Luscombe, N. M., Rot, G., Zupan, B., Curk, T., & Ule, J. (2010) · PLoS Biology · doi:10.1371/journal.pbio.1000530 · Cited by 242 · see citing works
Self-citationThe RNA-binding protein HuD regulates neuronal cell identity and maturation
Akamatsu, W., Fujihara, H., Mitsuhashi, T., Yano, M., Shibata, S., Hayakawa, Y., Okano, H. J., Sakakibara, S.-I., Takano, H., Takano, T., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407523102 · Cited by 222 · see citing works
Self-citationLicatalosi, D. D., Yano, M., Fak, J. J., Mele, A., Grabinski, S. E., Zhang, C., & Darnell, R. B. (2012) · Genes & Development · doi:10.1101/gad.191338.112 · Cited by 193 · see citing works
Self-citationKoushika, S. P., Lisbin, M. J., & White, K. (1996) · Current Biology · doi:10.1016/s0960-9822(02)70787-2 · Cited by 181 · see citing works
RNA binding proteins and the regulation of neuronal synaptic plasticity
Ule, J., & Darnell, R. B. (2006) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2006.01.003 · Cited by 177 · see citing works
Self-citationNova2 Regulates Neuronal Migration through an RNA Switch in Disabled-1 Signaling
Yano, M., Hayakawa-Yano, Y., Mele, A., & Darnell, R. B. (2010) · Neuron · doi:10.1016/j.neuron.2010.05.007 · Cited by 176 · see citing works
Self-citationMcKee, A. E., Minet, E., Stern, C., Riahi, S., Stiles, C. D., & Silver, P. A. (2005) · BMC Developmental Biology · doi:10.1186/1471-213x-5-14 · Cited by 166 · see citing works
Huang, C. S., Shi, S.-H., Ule, J., Ruggiu, M., Barker, L. A., Darnell, R. B., Jan, Y. N., & Jan, L. Y. (2005) · Cell · doi:10.1016/j.cell.2005.07.033 · Cited by 157 · see citing works
Self-citationCLIP: Crosslinking and ImmunoPrecipitation of In Vivo RNA Targets of RNA-Binding Proteins
Jensen, K. B., & Darnell, R. B. (2008) · Methods in molecular biology · doi:10.1007/978-1-60327-475-3_6 · Cited by 143 · see citing works
Self-citationMasson, J., Darmon, M. C., Conjard‐Duplany, A., Chuhma, N., Ropert, N., Thoby‐Brisson, M., Foutz, A. S., Parrot, S., Miller, G. M., Jorisch, R., et al. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.4241-05.2006 · Cited by 131 · see citing works
Bolognani, F., Contente-Cuomo, T., & Perrone-Bizzozero, N. I. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkp863 · Cited by 113 · see citing works
Ruggiu, M., Herbst, R., Kim, N., Jevsek, M., Fak, J. J., Mann, M. A., Fischbach, G., Burden, S. J., & Darnell, R. B. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813112106 · Cited by 113 · see citing works
Self-citationLisbin, M. J., Qiu, J., & White, K. (2001) · Genes & Development · doi:10.1101/gad.903101 · Cited by 97 · see citing works
ELAV inhibits 3′-end processing to promote neural splicing of <i>ewg</i> pre-mRNA
Soller, M., & White, K. (2003) · Genes & Development · doi:10.1101/gad.1106703 · Cited by 89 · see citing works
Das, D., Clark, T. A., Schweitzer, A. C., Yamamoto, M. L., Marr, H., Arribere, J., Minovitsky, S., Poliakov, A., Dubchak, I. L., Blume, J. E., et al. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm485 · Cited by 89 · see citing works
Regulation of Neuron-Specific Alternative Splicing of Neurofibromatosis Type 1 Pre-mRNA
Zhu, H., Hinman, M. N., Hasman, R. A., Mehta, P., & Lou, H. J. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01509-07 · Cited by 82 · see citing works
Wang, J., & Bell, L. R. (1994) · Genes & Development · doi:10.1101/gad.8.17.2072 · Cited by 80 · see citing works
Koushika, S. P., Soller, M., & White, K. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.5.1836-1845.2000 · Cited by 73 · see citing works
Calarco, J. A., Zhen, M., & Blencowe, B. J. (2011) · RNA · doi:10.1261/rna.2603911 · Cited by 72 · see citing works
ELAV Multimerizes on Conserved AU 4-6 Motifs Important for ewg Splicing Regulation
Soller, M., & White, K. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.17.7580-7591.2005 · Cited by 67 · see citing works
Renal response to metabolic acidosis: Role of mRNA stabilization
Ibrahim, H., Lee, Y. J., & Curthoys, N. P. (2007) · Kidney International · doi:10.1038/sj.ki.5002581 · Cited by 60 · see citing works
Promotion of exon 6 inclusion in HuD pre-mRNA by Hu protein family members
Wang, H., Molfenter, J., Zhu, H., & Lou, H. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq028 · Cited by 49 · see citing works
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Altman, B. J., Stine, Z. E., & Dang, C. V. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.71 · Cited by 2,119 · see citing works
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Fu, X.-D., & Ares, M. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3778 · Cited by 1,044 · see citing works
Raj, B., & Blencowe, B. J. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.004 · Cited by 475 · see citing works
Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders
Johmura, Y., Yamanaka, T., Omori, S., Wang, T.-W., Sugiura, Y., Matsumoto, M., Suzuki, N., Kumamoto, S., Yamaguchi, K., Hatakeyama, S., et al. (2021) · Science · doi:10.1126/science.abb5916 · Cited by 440 · see citing works
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Getting to the cores of autism
Iakoucheva, L. M., Muotri, A. R., & Sebat, J. (2019) · Cell · doi:10.1016/j.cell.2019.07.037 · Cited by 260 · see citing works
Moore, M. J., Zhang, C., Gantman, E. C., Mele, A., Darnell, J. C., & Darnell, R. B. (2014) · Nature Protocols · doi:10.1038/nprot.2014.012 · Cited by 251 · see citing works
Self-citationCytoplasmic Rbfox1 Regulates the Expression of Synaptic and Autism-Related Genes
Lee, J.-A., Damianov, A., Lin, C.-H., Fontes, M., Parikshak, N. N., Anderson, E. S., Geschwind, D. H., Black, D. L., & Martin, K. C. (2016) · Neuron · doi:10.1016/j.neuron.2015.11.025 · Cited by 232 · see citing works
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Darnell, R. B. (2013) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-062912-114322 · Cited by 181 · see citing works
Self-citationLi, Q., Zheng, S., Han, A., Lin, C.-H., Stoilov, P., Fu, X.-D., & Black, D. L. (2014) · eLife · doi:10.7554/elife.01201 · Cited by 174 · see citing works
Quesnel-Vallières, M., Dargaei, Z., Irimia, M., Gonatopoulos-Pournatzis, T., Ip, J. Y., Wu, M., Sterne-Weiler, T., Nakagawa, S., Woodin, M. A., Blencowe, B. J., et al. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.11.033 · Cited by 178 · see citing works
Bowles, K. R., Silva, M. C., Whitney, K., Bertucci, T., Berlind, J. E., Lai, J. D., Garza, J. C., Boles, N. C., Mahali, S., Strang, K. H., et al. (2021) · Cell · doi:10.1016/j.cell.2021.07.003 · Cited by 175 · see citing works
Bronicki, L. M., & Jasmin, B. J. (2013) · RNA · doi:10.1261/rna.039164.113 · Cited by 126 · see citing works
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- Authors
- Ince-Dunn, G., Okano, H. J., Jensen, K. B., Park, W.-Y., Zhong, R., Ule, J., Mele, A., Fak, J. J., Yang, C., Zhang, C., Yoo, J., Herre, M., Okano, H., Noebels, J. L., & Darnell, R. B.
- Affiliations
- Rockefeller University (US)
- Keio University (JP)
- Baylor College of Medicine (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Darnell, Robert B.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 75
- Issue
- 6
- Pages
- 1067-1080
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3517991
- OpenAlex
- W2086474057
- Cited by
- 212
- References
- 58
- Citations by year
- 2026: 12 · 2025: 8 · 2024: 14 · 2023: 13 · 2022: 16 · 2021: 20 · 2020: 13 · 2019: 14 · 2018: 16 · 2017: 11 · 2016: 21 · 2015: 21 · 2014: 20 · 2013: 13
- FWCI
- 6.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Wellcome Trust (089701)
- National Institute of General Medical Sciences (K99 GM95713, K99GM095713, R00GM095713)
- National Institute of Neurological Disorders and Stroke (R01NS081706, NS34389, R01NS034389, R56NS034389, NS29709, R01NS029709)
- National Center for Research Resources (UL1RR024143)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 24064, P30HD024064)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- HU protein, RNA-binding proteins, alternative splicing, 3' UTR regulation, glutamate synthesis, neuronal excitability, AU-rich elements, excitation-inhibition balance, spontaneous seizures, HITS-CLIP
- MeSH terms
- Animals, Animals, Newborn, Brain, Disease Models, Animal, Electroencephalography, Epilepsy, Gene Expression Regulation, Glutaminase, Nerve Tissue Proteins, Neurons, RNA Splicing, RNA, Messenger, RNA-Binding Proteins, Mice, Knockout, Glutamic Acid, Computational Biology, 3' Untranslated Regions, Microarray Analysis, Mice, ELAV Proteins
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 ›
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