Genome-wide Analysis of Alternative Pre-mRNA Splicing and RNA-Binding Specificities of the Drosophila hnRNP A/B Family Members
Open accessAbstract
Heterogeneous nuclear ribonucleoproteins (hnRNPs) have been traditionally seen as proteins packaging RNA nonspecifically into ribonucleoprotein particles (RNPs), but evidence suggests specific cellular functions on discrete target pre-mRNAs. Here we report genome-wide analysis of alternative splicing patterns regulated by four Drosophila homologs of the mammalian hnRNP A/B family (hrp36, hrp38, hrp40, and hrp48). Analysis of the global RNA-binding distributions of each protein revealed both small and extensively bound regions on target transcripts. A significant subset of RNAs were bound and regulated by more than one hnRNP protein, revealing a combinatorial network of interactions. In vitro RNA-binding site selection experiments (SELEX) identified distinct binding motif specificities for each protein, which were overrepresented in their respective regulated and bound transcripts. These results indicate that individual heterogeneous ribonucleoproteins have specific affinities for overlapping, but distinct, populations of target pre-mRNAs controlling their patterns of RNA processing.
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?
Very different motifs have been previously described for different HNRNPA family members from human and Drosophila, whereas RNAcompete motifs for the same proteins are closely related.
“very different motifs have been previously described for different HNRNPA family members from human and Drosophila19–22, whereas the RNAcompete motifs for the same proteins are closely related”
From A compendium of RNA-binding motifs for decoding gene regulation (2013) · cites this paper as [21]
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
WebLogo: A Sequence Logo Generator: Figure 1Preprint
Crooks, G. E., Hon, G. C., Chandonia, J., & Brenner, S. E. (2004) · Genome Research · doi:10.1101/gr.849004 · Cited by 12,433 · see citing works
Self-citationAlternative 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
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
Listening to silence and understanding nonsense: exonic mutations that affect splicing
Cartegni, L., Chew, S. L., & Krainer, A. R. (2002) · Nature Reviews Genetics · doi:10.1038/nrg775 · Cited by 2,209 · see citing works
Messenger-RNA-binding proteins and the messages they carry
Dreyfuss, G., Kim, V. N., & Kataoka, N. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm760 · Cited by 1,469 · see citing works
HITS-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 4× · see citing works
“These findings suggest a preferential binding site location for a given factor controlling a specific splice event, as seen previously (Aznarez et al., 2008; Ben-Dov et al., 2008; Blanchette et al., 2005; Castle et al., 2008; Licatalosi et al., 2008; Ule et al., 2006; Zhang et al., 2008).”
InfluentialTranscription regulation and animal diversity
Levine, M., & Tjian, R. (2003) · Nature · doi:10.1038/nature01763 · Cited by 1,309 · see citing works
Understanding alternative splicing: towards a cellular code
Matlin, A. J., Clark, F., & Smith, C. W. J. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1645 · Cited by 1,299 · see citing works
Alternative Splicing: New Insights from Global Analyses
Blencowe, B. J. (2006) · Cell · doi:10.1016/j.cell.2006.06.023 · Cited by 1,122 · see citing works
FatiGO: a web tool for finding significant associations of Gene Ontology terms with groups of genes
Al‐Shahrour, F., Díaz‐Uriarte, R., & Dopazo, J. (2004) · Bioinformatics · doi:10.1093/bioinformatics/btg455 · Cited by 1,118 · see citing works
Alternative pre-mRNA splicing: the logic of combinatorial control
Smith, C. W. J., & Valcárcel, J. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)01604-2 · Cited by 901 · see citing works
hnRNP complexes: composition, structure, and function
Krecic, A. M., & Swanson, M. S. (1999) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(99)80051-9 · Cited by 813 · see citing works
Regulation of alternative pre-mRNA splicing by hnRNP A1 and splicing factor SF2
Mayeda, A., & Krainer, A. R. (1992) · Cell · doi:10.1016/0092-8674(92)90477-t · Cited by 735 · see citing works
Regulation of Alternative Splicing in Vivo by Overexpression of Antagonistic Splicing Factors
Cáceres, J. F., Stamm, S., Helfman, D. M., & Krainer, A. R. (1994) · Science · doi:10.1126/science.8085156 · Cited by 619 · see citing works
Genomic variants in exons and introns: identifying the splicing spoilers
Pagani, F., & Baralle, F. E. (2004) · Nature Reviews Genetics · doi:10.1038/nrg1327 · Cited by 601 · 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
Transcription Factors Bind Thousands of Active and Inactive Regions in the Drosophila Blastoderm
Li, X., MacArthur, S., Bourgon, R., Nix, D. A., Pollard, D. A., Iyer, V. N., Hechmer, A., Simirenko, L., Stapleton, M., Hendriks, C. L. L., et al. (2008) · eScholarship (California Digital Library) · doi:10.1371/journal.pbio.0060027 · Cited by 479 · see citing works
Self-citationZhu, J., Mayeda, A., & Krainer, A. R. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00409-9 · Cited by 396 · see citing works
Regulation of gene expression by alternative untranslated regions
Hughes, T. A. (2006) · Trends in Genetics · doi:10.1016/j.tig.2006.01.001 · Cited by 338 · see citing works
Function of conserved domains of hnRNP A1 and other hnRNP A/B proteins.
Mayeda, A., Munroe, S. H., Cáceres, J. F., & Krainer, A. R. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06883.x · Cited by 329 · 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
Goren, A., Ram, O., Amit, M., Keren, H., Lev-Maor, G., Vig, I., Pupko, T., & Ast, G. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.05.008 · Cited by 301 · see citing works
Defining 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
Zeitlinger, J., Zinzen, R. P., Stark, A., Kellis, M., Zhang, H., Young, R. A., & Levine, M. (2007) · Genes & Development · doi:10.1101/gad.1509607 · Cited by 286 · see citing works
hnRNP A/B proteins are required for inhibition of HIV‐1 pre‐mRNA splicing
Caputi, M., Mayeda, A., Krainer, A. R., & Zahler, A. M. (1999) · The EMBO Journal · doi:10.1093/emboj/18.14.4060 · Cited by 258 · see citing works
Mayeda, A., Helfman, D. M., & Krainer, A. R. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.5.2993 · Cited by 242 · see citing works
Intronic Binding Sites for hnRNP A/B and hnRNP F/H Proteins Stimulate Pre-mRNA Splicing
Martínez-Contreras, R. D., Fisette, J., Nasim, F., Madden, R., Cordeau, M., & Chabot, B. (2006) · PLoS Biology · doi:10.1371/journal.pbio.0040021 · Cited by 226 · see citing works
Blanchette, M., & Chabot, B. (1999) · The EMBO Journal · doi:10.1093/emboj/18.7.1939 · Cited by 205 · see citing works
Self-citationEperon, I. C., Makarova, O. V., Mayeda, A., Munroe, S. H., Cáceres, J. F., Hayward, D., & Krainer, A. R. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.22.8303-8318.2000 · Cited by 201 · see citing works
General and Specific Functions of Exonic Splicing Silencers in Splicing Control
Wang, Z., Xiao, X. G., Nostrand, E. L. V., & Burge, C. B. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.05.018 · Cited by 189 · see citing works
Manak, J. R., Dike, S., Sementchenko, V. I., Kapranov, P., Biemar, F., Long, J. C., Cheng, J., Bell, I., Ghosh, S., Piccolboni, A., et al. (2006) · Nature Genetics · doi:10.1038/ng1875 · Cited by 182 · see citing works
Fitzwater, T., & Polisky, B. A. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)67019-0 · Cited by 174 · see citing works
Regulation of Alternative Splicing: More than Just the ABCs
House, A. E., & Lynch, K. W. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.r700031200 · Cited by 173 · see citing works
Computational Models for Neurogenic Gene Expression in the Drosophila Embryo
Zinzen, R. P., Senger, K., Levine, M., & Papatsenko, D. (2006) · Current Biology · doi:10.1016/j.cub.2006.05.044 · Cited by 165 · see citing works
Norvell, A., Kelley, R. L., Wehr, K., et al. (1999) · Genes & Development · doi:10.1101/gad.13.7.864 · Cited by 161 · see citing works
Genome-wide Analysis of Alternative Pre-mRNA Splicing
Ben-Dov, C., Hartmann, B., Lundgren, J., & Valcárcel, J. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.r700033200 · Cited by 151 · see citing works
Zahler, A. M., Damgaard, C. K., Kjems, J., & Caputi, M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312743200 · Cited by 145 · see citing works
Global analysis of positive and negative pre-mRNA splicing regulators in DrosophilaPreprint
Blanchette, M., Green, R. E., Brenner, S. E., & Rio, D. C. (2005) · Genes & Development · doi:10.1101/gad.1314205 · Cited by 124 · see citing works
Self-citationBilodeau, P. S., Domsic, J. K., Mayeda, A., et al. (2001) · Journal of Virology · doi:10.1128/jvi.75.18.8487-8497.2001 · Cited by 119 · see citing works
A regulator of Dscam mutually exclusive splicing fidelity
Olson, S., Blanchette, M., Park, J., Savva, Y. A., Yeo, G. W.-M., Yeakley, J. M., Rio, D. C., & Graveley, B. R. (2007) · Nature Structural & Molecular Biology · doi:10.1038/nsmb1339 · Cited by 96 · see citing works
Self-citationAznarez, I., Barash, Y., Shai, O., He, D., Zielenski, J., Tsui, L., Parkinson, J., Frey, B. J., Rommens, J. M., & Blencowe, B. J. (2008) · Genome Research · doi:10.1101/gr.073155.107 · Cited by 94 · see citing works
Nasim, F., HUTCHISON, S., Cordeau, M., & Chabot, B. (2002) · RNA · doi:10.1017/s1355838202024056 · Cited by 89 · see citing works
Hutchison, S., LeBel, C., Blanchette, M., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203633200 · Cited by 85 · see citing works
Self-citationDomsic, J. K., Wang, Y., Mayeda, A., et al. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.23.8762-8772.2003 · Cited by 72 · see citing works
Hammond, L. E., Rudner, D. Z., Kanaar, R., et al. (1997) · Molecular and Cellular Biology · doi:10.1128/mcb.17.12.7260 · Cited by 65 · see citing works
TheDrosophila Hrb87Fgene encodes a new member of the A and B hnRNP protein group
Haynes, S. R., Johnson, D. E., Raychaudhuri, G., et al. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.1.25 · Cited by 63 · see citing works
Amarasinghe, A. K., MacDiarmid, R. M., Adams, M. D., & Rio, D. C. (2001) · RNA · doi:10.1017/s1355838201010603 · Cited by 32 · see citing works
Self-citationZu, K., Sikes, M. L., Haynes, S. R., et al. (1996) · Molecular Biology of the Cell · doi:10.1091/mbc.7.7.1059 · Cited by 31 · see citing works
Separable roles in vivo for the two RNA binding domains of a Drosophila A1-hnRNP homolog
Zu, K., Sikes, M. L., & Beyer, A. L. (1998) · RNA · doi:10.1017/s135583829898102x · Cited by 25 · see citing works
Piñol-Roma, S., Swanson, M. S., Matunis, M. J., et al. (1990) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(90)81133-f · Cited by 24 · see citing works
Exon skipping by overexpression of a Drosophila heterogeneous nuclear ribonucleoprotein in vivo.
Shen, J., Zu, K., Cass, C. L., et al. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.6.1822 · Cited by 21 · see citing works
Conservation patterns in different functional sequence categories of divergent Drosophila \nspecies
Papatsenko, D., Kislyuk, A. O., Levine, M., & Dubchak, I. L. (2005) · eScholarship (California Digital Library) · Cited by 20 · see citing works
Conservation patterns in different functional sequence categories of divergent Drosophila species
Papatsenko, D., Kislyuk, A. O., Levine, M., et al. (2006) · Genomics · doi:10.1016/j.ygeno.2006.03.012
Flagged first, then by citations
Cited by
Sorted by citations
A compendium of RNA-binding motifs for decoding gene regulation
Ray, D., Kazan, H., Cook, K. B., Weirauch, M. T., Najafabadi, H. S., Li, X., Gueroussov, S., Albu, M., Zheng, H., Yang, A., et al. (2013) · Nature · doi:10.1038/nature12311 · Cited by 1,480 · see citing works
Mechanisms and Regulation of Alternative Pre-mRNA Splicing
Lee, Y., & Rio, D. C. (2015) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-034316 · Cited by 1,291 · see citing works
Self-citationMechanisms of alternative splicing regulation: insights from molecular and genomics approaches
Chen, M., & Manley, J. L. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2777 · Cited by 1,284 · see citing works
Huelga, S. C., Vu, A. Q., Arnold, J. D., Liang, T. Y., Liu, P. P., Yan, B. Y., Donohue, J. P., Shiue, L., Hoon, S., Brenner, S., et al. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.02.001 · Cited by 470 · see citing works
Self-citationAlternative splicing: decoding an expansive regulatory layer
Irimia, M., & Blencowe, B. J. (2012) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2012.03.005 · Cited by 177 · see citing works
Current-generation high-throughput sequencing: deepening insights into mammalian transcriptomes
Blencowe, B. J., Ahmad, S., & Lee, L. J. (2009) · Genes & Development · doi:10.1101/gad.1788009 · Cited by 168 · see citing works
- Authors
- Blanchette, M., Green, R. E., MacArthur, S., Brooks, A. N., Brenner, S. E., Eisen, M. B., & Rio, D. C.
- Affiliations
- University of California, Berkeley (US)
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Blanchette, Marco
- Rio, Donald C.
- ORCID
- Venue
- Molecular Cell
- Publisher
- Elsevier BV
- Published
- 2009-02
- Volume
- 33
- Issue
- 4
- Pages
- 438-449
- ISSN
- 1097-2765 (ISSN-L)
- PMC
- PMC2674966
- OpenAlex
- W2103823160
- Cited by
- 86
- References
- 54
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 2 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 5 · 2017: 6 · 2016: 5 · 2015: 7 · 2014: 7 · 2013: 7 · 2012: 9
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Molecular Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Human Genome Research Institute (U01HG004271)
- National Institute of General Medical Sciences (R01GM061987, R01 GM61987, R01GM071655)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- hnRNP A/B, alternative splicing, RNA-binding proteins, Drosophila, SELEX, RNA-binding motif, ribonucleoprotein particles
- MeSH terms
- Animals, Base Sequence, Binding Sites, Cells, Cultured, Drosophila, Molecular Sequence Data, RNA Precursors, RNA, Messenger, Alternative Splicing, Heterogeneous-Nuclear Ribonucleoprotein Group A-B, Genome, Insect
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