rna splice sites


Summary: Nucleotide sequences located at the ends of EXONS and recognized in pre-messenger RNA by SPLICEOSOMES. They are joined during the RNA SPLICING reaction, forming the junctions between exons.

Top Publications

  1. Crawford D, Hoskins A, Friedman L, Gelles J, Moore M. Single-molecule colocalization FRET evidence that spliceosome activation precedes stable approach of 5' splice site and branch site. Proc Natl Acad Sci U S A. 2013;110:6783-8 pubmed publisher
    ..Separation of the sites of chemistry until very late in the splicing pathway may be crucial for preventing splicing at incorrect sites. ..
  2. Bradley R, Merkin J, Lambert N, Burge C. Alternative splicing of RNA triplets is often regulated and accelerates proteome evolution. PLoS Biol. 2012;10:e1001229 pubmed publisher
  3. Delgado E, Carrera C, Nebreda P, Fernandez Garcia A, Pinilla M, García V, et al. Identification of new splice sites used for generation of rev transcripts in human immunodeficiency virus type 1 subtype C primary isolates. PLoS ONE. 2012;7:e30574 pubmed publisher
    ..Usage of the newly identified splice sites is consistent with sequence features commonly found in subtype C viruses. These results show that splice site usage may differ between HIV-1 subtypes. ..
  4. Janas M, Khaled M, Schubert S, Bernstein J, Golan D, Veguilla R, et al. Feed-forward microprocessing and splicing activities at a microRNA-containing intron. PLoS Genet. 2011;7:e1002330 pubmed publisher
    ..Our data demonstrate novel mutually-cooperative microprocessing and splicing activities at an intronic miRNA locus and suggest that the initiation of spliceosome assembly may promote microprocessing of intronic miRNAs. ..
  5. Kameyama T, Suzuki H, Mayeda A. Re-splicing of mature mRNA in cancer cells promotes activation of distant weak alternative splice sites. Nucleic Acids Res. 2012;40:7896-906 pubmed publisher
    ..The re-splicing of mature mRNA can potentially generate mutation-independent diversity in cancer transcriptomes. Conversely, a mechanism may exist in normal cells to prevent potentially deleterious mRNA re-splicing events. ..
  6. Moss W, Dela Moss L, Kierzek E, Kierzek R, Priore S, Turner D. The 3' splice site of influenza A segment 7 mRNA can exist in two conformations: a pseudoknot and a hairpin. PLoS ONE. 2012;7:e38323 pubmed publisher
    ..The results suggest that segment 7 mRNA splicing can be controlled by a conformational switch that exposes or hides the splice site. ..
  7. Frühwald J, Camacho Londoño J, Dembla S, Mannebach S, Lis A, Drews A, et al. Alternative splicing of a protein domain indispensable for function of transient receptor potential melastatin 3 (TRPM3) ion channels. J Biol Chem. 2012;287:36663-72 pubmed publisher
    ..We conclude that TRPM3?ICF variants are regulatory channel subunits fine-tuning TRPM3 channel activity. ..
  8. Yenerall P, Zhou L. Identifying the mechanisms of intron gain: progress and trends. Biol Direct. 2012;7:29 pubmed publisher
    ..Finally, because these proposed mechanisms fail to explain the mechanistic origin of many recently gained introns, we also look at trends that may aid researchers in identifying other potential mechanism(s) of intron gain. ..
  9. Khodor Y, Menet J, Tolan M, Rosbash M. Cotranscriptional splicing efficiency differs dramatically between Drosophila and mouse. RNA. 2012;18:2174-86 pubmed publisher
    ..The gene length and distance effects indicate that more "nascent time" gives rise to greater cotranscriptional splicing efficiency in both systems. ..

More Information


  1. Pervouchine D, Knowles D, Guigo R. Intron-centric estimation of alternative splicing from RNA-seq data. Bioinformatics. 2013;29:273-4 pubmed publisher
    ..The C code of bam2ssj is open source and is available at https://github.com/pervouchine/bam2ssj dp@crg.eu ..
  2. Merkin J, Russell C, Chen P, Burge C. Evolutionary dynamics of gene and isoform regulation in Mammalian tissues. Science. 2012;338:1593-9 pubmed publisher
    ..Our data also indicate that alternative splicing often alters protein phosphorylatability, delimiting the scope of kinase signaling. ..
  3. Moss W, Dela Moss L, Priore S, Turner D. The influenza A segment 7 mRNA 3' splice site pseudoknot/hairpin family. RNA Biol. 2012;9:1305-10 pubmed publisher
    ..A measure of stability of the structures also shows interesting trends with respect to host specificity: avian strains tend to be the most stable, followed by swine and then human. ..
  4. Zhang Y, Lameijer E, t Hoen P, Ning Z, Slagboom P, Ye K. PASSion: a pattern growth algorithm-based pipeline for splice junction detection in paired-end RNA-Seq data. Bioinformatics. 2012;28:479-86 pubmed publisher
    ..In addition, our package can discover differential and shared splicing patterns among multiple samples. The code and utilities can be freely downloaded from https://trac.nbic.nl/passion and ftp://ftp.sanger.ac.uk/pub/zn1/passion. ..
  5. Passoni M, De Conti L, Baralle M, Buratti E. UG repeats/TDP-43 interactions near 5' splice sites exert unpredictable effects on splicing modulation. J Mol Biol. 2012;415:46-60 pubmed publisher
    ..The general rule that can be drawn at the moment is that the importance of UG repeats near 5' splice sites should always be experimentally validated on a case-by-case basis. ..
  6. Roca X, Krainer A, Eperon I. Pick one, but be quick: 5' splice sites and the problems of too many choices. Genes Dev. 2013;27:129-44 pubmed publisher
  7. Refaat M, Lubitz S, Makino S, Islam Z, Frangiskakis J, Mehdi H, et al. Genetic variation in the alternative splicing regulator RBM20 is associated with dilated cardiomyopathy. Heart Rhythm. 2012;9:390-6 pubmed publisher
    ..58; P = .047). Mutations in RBM20 were observed in approximately 3% of subjects with DCM. There were no differences in survival, transplantation rate, and frequency of ICD therapy in mutation carriers. ..
  8. Hodson M, Hudson A, Cherny D, Eperon I. The transition in spliceosome assembly from complex E to complex A purges surplus U1 snRNPs from alternative splice sites. Nucleic Acids Res. 2012;40:6850-62 pubmed publisher
    ..We propose a mechanism for selection of the 5' splice site. Our results show that constitutive splicing components need not be present in a fixed stoichiometry in a splicing complex. ..
  9. Rogozin I, Carmel L, Csuros M, Koonin E. Origin and evolution of spliceosomal introns. Biol Direct. 2012;7:11 pubmed publisher
  10. Szcześniak M, Kabza M, Pokrzywa R, Gudys A, Makałowska I. ERISdb: a database of plant splice sites and splicing signals. Plant Cell Physiol. 2013;54:e10 pubmed publisher
    ..All the data are stored in a novel database called ERISdb and are freely available at http://lemur.amu.edu.pl/share/ERISdb/. ..
  11. Amit M, Donyo M, Hollander D, Goren A, Kim E, Gelfman S, et al. Differential GC content between exons and introns establishes distinct strategies of splice-site recognition. Cell Rep. 2012;1:543-56 pubmed publisher
  12. Barbosa Morais N, Irimia M, Pan Q, Xiong H, Gueroussov S, Lee L, et al. The evolutionary landscape of alternative splicing in vertebrate species. Science. 2012;338:1587-93 pubmed publisher
    ..These events likely further contributed to the diversification of splicing and other transcriptomic changes that underlie phenotypic differences among vertebrate species. ..
  13. Li Y, Li Byarlay H, Burns P, Borodovsky M, Robinson G, Ma J. TrueSight: a new algorithm for splice junction detection using RNA-seq. Nucleic Acids Res. 2013;41:e51 pubmed publisher
    ..By utilizing gene models improved by TrueSight, we characterized AS types in honey bee transcriptome. We believe that TrueSight will be highly useful to comprehensively study the biology of alternative splicing. ..
  14. Langemeier J, Schrom E, Rabner A, Radtke M, Zychlinski D, Saborowski A, et al. A complex immunodeficiency is based on U1 snRNP-mediated poly(A) site suppression. EMBO J. 2012;31:4035-44 pubmed publisher
    ..Moreover, our data endorse the recently described role of U1 snRNP in suppression of intronic poly(A) sites, which is here deleterious for p14 mRNA biogenesis. ..
  15. Ortuño Pineda C, Galindo Rosales J, Calderón Salinas J, Villegas Sepúlveda N, Saucedo Cardenas O, De Nova Ocampo M, et al. Binding of hnRNP H and U2AF65 to respective G-codes and a poly-uridine tract collaborate in the N50-5'ss selection of the REST N exon in H69 cells. PLoS ONE. 2012;7:e40315 pubmed publisher
    ..Our results evidenced novel hnRNP H and U2AF65 functions: respectively, U2AF65-recruiting to a 5'ss in humans and the hnRNP H-displacing function from two juxtaposed GGGG codes. ..
  16. Avendaño Vázquez S, Dhir A, Bembich S, Buratti E, Proudfoot N, Baralle F. Autoregulation of TDP-43 mRNA levels involves interplay between transcription, splicing, and alternative polyA site selection. Genes Dev. 2012;26:1679-84 pubmed publisher
    ..Overall, we uncover complex interplay between transcription, splicing, and 3' end processing to effect autoregulation of TDP-43. ..
  17. Al Ayoubi A, Zheng H, Liu Y, Bai T, Eblen S. Mitogen-activated protein kinase phosphorylation of splicing factor 45 (SPF45) regulates SPF45 alternative splicing site utilization, proliferation, and cell adhesion. Mol Cell Biol. 2012;32:2880-93 pubmed publisher
    ..These data identify SPF45 as the first splicing factor regulated by multiple MAP kinase pathways and show effects of both SPF45 overexpression and phosphorylation. ..
  18. Wang E, Cody N, Jog S, Biancolella M, Wang T, Treacy D, et al. Transcriptome-wide regulation of pre-mRNA splicing and mRNA localization by muscleblind proteins. Cell. 2012;150:710-24 pubmed publisher
    ..These findings hold several new implications for DM pathogenesis. ..
  19. Harrow J, Frankish A, Gonzalez J, Tapanari E, Diekhans M, Kokocinski F, et al. GENCODE: the reference human genome annotation for The ENCODE Project. Genome Res. 2012;22:1760-74 pubmed publisher
    ..GENCODE 7 is publicly available from gencodegenes.org and via the Ensembl and UCSC Genome Browsers. ..
  20. Sanders S, Murtha M, Gupta A, Murdoch J, Raubeson M, Willsey A, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature. 2012;485:237-41 pubmed publisher
  21. Query C, Konarska M. CEF1/CDC5 alleles modulate transitions between catalytic conformations of the spliceosome. RNA. 2012;18:1001-13 pubmed publisher
  22. Zarnack K, König J, Tajnik M, Martincorena I, Eustermann S, Stévant I, et al. Direct competition between hnRNP C and U2AF65 protects the transcriptome from the exonization of Alu elements. Cell. 2013;152:453-66 pubmed publisher
    ..Thus, by preventing U2AF65 binding to Alu elements, hnRNP C plays a critical role as a genome-wide sentinel protecting the transcriptome. The findings have important implications for human evolution and disease. ..
  23. De Conti L, Baralle M, Buratti E. Exon and intron definition in pre-mRNA splicing. Wiley Interdiscip Rev RNA. 2013;4:49-60 pubmed publisher
    ..Therefore, it is expected that future challenges in splicing research will be the careful characterization of all these influences to improve our ability to predict splicing choices in different organisms or in specific contexts. ..
  24. Wu J, Anczukow O, Krainer A, Zhang M, Zhang C. OLego: fast and sensitive mapping of spliced mRNA-Seq reads using small seeds. Nucleic Acids Res. 2013;41:5149-63 pubmed publisher
    ..OLego is freely available at http://zhanglab.c2b2.columbia.edu/index.php/OLego. ..
  25. Ma L, Tan Z, Teng Y, Hoersch S, Horvitz H. In vivo effects on intron retention and exon skipping by the U2AF large subunit and SF1/BBP in the nematode Caenorhabditis elegans. RNA. 2011;17:2201-11 pubmed publisher
    ..Our study provides in vivo evidence that intron retention and exon skipping can be regulated largely by the identities of 3' splice sites. ..
  26. Tavanez J, Madl T, Kooshapur H, Sattler M, Valcarcel J. hnRNP A1 proofreads 3' splice site recognition by U2AF. Mol Cell. 2012;45:314-29 pubmed publisher
    ..Consistent with the functional relevance of this activity for splicing, proofreading assays reveal a role for hnRNP A1 in U2AF-mediated recruitment of U2 snRNP to the pre-mRNA. ..
  27. Hartmann L, Neveling K, Borkens S, Schneider H, Freund M, Grassman E, et al. Correct mRNA processing at a mutant TT splice donor in FANCC ameliorates the clinical phenotype in patients and is enhanced by delivery of suppressor U1 snRNAs. Am J Hum Genet. 2010;87:480-93 pubmed publisher
  28. Keating K, Toor N, Perlman P, Pyle A. A structural analysis of the group II intron active site and implications for the spliceosome. RNA. 2010;16:1-9 pubmed publisher
    ..This analysis leads to a set of predictions for the molecular structure of the spliceosomal active site. ..
  29. Brosseau J, Lucier J, Lapointe E, Durand M, Gendron D, Gervais Bird J, et al. High-throughput quantification of splicing isoforms. RNA. 2010;16:442-9 pubmed publisher
    ..Using this pipeline it is now possible to rapidly identify splicing isoform signatures in different types of human tissues or to validate complete sets of data generated by microarray expression profiling and deep sequencing techniques. ..
  30. Gu Z, Ji B, Wan C, He G, Zhang J, Zhang M, et al. A splice site mutation in CRYBA1/A3 causing autosomal dominant posterior polar cataract in a Chinese pedigree. Mol Vis. 2010;16:154-60 pubmed
    ..The same mutation in this gene had previously been reported to be associated with other phenotype cataracts. This study is the first report relating a mutation of CRYBA1/A3 to posterior polar cataract. ..
  31. Geranmayeh F, Clement E, Feng L, Sewry C, Pagan J, Mein R, et al. Genotype-phenotype correlation in a large population of muscular dystrophy patients with LAMA2 mutations. Neuromuscul Disord. 2010;20:241-50 pubmed publisher
    ..This large study identified novel LAMA2 mutations and highlights the role of immunohistochemical studies for merosin status in predicting clinical severity of MDC1A. ..
  32. Au K, Jiang H, Lin L, Xing Y, Wong W. Detection of splice junctions from paired-end RNA-seq data by SpliceMap. Nucleic Acids Res. 2010;38:4570-8 pubmed publisher
    ..Compared to current methods, SpliceMap can achieve 12% higher sensitivity without sacrificing specificity. ..
  33. Sinha R, Lenser T, Jahn N, Gausmann U, Friedel S, Szafranski K, et al. TassDB2 - A comprehensive database of subtle alternative splicing events. BMC Bioinformatics. 2010;11:216 pubmed publisher
    ..TassDB2, available via http://www.tassdb.info, provides comprehensive resources for researchers interested in both targeted experimental studies and large-scale bioinformatics analyses of short distance tandem splice sites. ..
  34. Kim D, Hahn Y. Identification of human-specific transcript variants induced by DNA insertions in the human genome. Bioinformatics. 2011;27:14-21 pubmed publisher
    ..The exaptation of human-specific genomic inserts as novel transcript variants may have increased human gene versatility or affected gene regulation. ..
  35. Farlow A, Meduri E, Schlotterer C. DNA double-strand break repair and the evolution of intron density. Trends Genet. 2011;27:1-6 pubmed publisher
    ..We propose a novel framework in which species-specific differences in the activity of NHEJ and homologous recombination (HR) during the repair of DSBs underlie changes in intron density. ..
  36. Glaus E, Schmid F, Da Costa R, Berger W, Neidhardt J. Gene therapeutic approach using mutation-adapted U1 snRNA to correct a RPGR splice defect in patient-derived cells. Mol Ther. 2011;19:936-41 pubmed publisher
    ..U1-based gene therapeutic approaches constitute promising technologies to treat SDS mutations in inherited diseases including X-linked RP. ..
  37. Corrionero A, Minana B, Valcarcel J. Reduced fidelity of branch point recognition and alternative splicing induced by the anti-tumor drug spliceostatin A. Genes Dev. 2011;25:445-59 pubmed publisher
    ..Our results reveal a mechanism that prevents nonproductive base-pairing interactions in the spliceosome, and highlight the regulatory and cancer therapeutic potential of perturbing the fidelity of splice site recognition. ..
  38. Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature. 2011;478:64-9 pubmed publisher
    ..Our results provide the first evidence indicating that genetic alterations of the major splicing components could be involved in human pathogenesis, also implicating a novel therapeutic possibility for myelodysplasia...
  39. Ke S, Shang S, KALACHIKOV S, Morozova I, Yu L, Russo J, et al. Quantitative evaluation of all hexamers as exonic splicing elements. Genome Res. 2011;21:1360-74 pubmed publisher
    ..This approach may prove of general use in defining nucleic acid regulatory motifs, substitute for functional SELEX in most cases, and provide insights about splicing mechanisms. ..
  40. Heiner M, Hui J, Schreiner S, Hung L, Bindereif A. HnRNP L-mediated regulation of mammalian alternative splicing by interference with splice site recognition. RNA Biol. 2010;7:56-64 pubmed
    ..In sum, our data provide new insights into the mechanisms of how hnRNP L-bound to intronic sites-regulates exon recognition. ..
  41. Casadei S, Norquist B, Walsh T, Stray S, Mandell J, Lee M, et al. Contribution of inherited mutations in the BRCA2-interacting protein PALB2 to familial breast cancer. Cancer Res. 2011;71:2222-9 pubmed publisher
    ..Given this mutation prevalence and risk, consideration might be given to clinical testing of PALB2 by complete genomic sequencing for familial breast cancer patients with wild-type sequences at BRCA1 and BRCA2. ..
  42. Kim S, Kim H, Fong N, Erickson B, Bentley D. Pre-mRNA splicing is a determinant of histone H3K36 methylation. Proc Natl Acad Sci U S A. 2011;108:13564-9 pubmed publisher
    ..These results suggest that the cotranscriptional splicing apparatus influences establishment of normal patterns of histone modification. ..
  43. Thomassen M, Blanco A, Montagna M, Hansen T, Pedersen I, Gutierrez Enriquez S, et al. Characterization of BRCA1 and BRCA2 splicing variants: a collaborative report by ENIGMA consortium members. Breast Cancer Res Treat. 2012;132:1009-23 pubmed publisher
    ..Importantly, this study demonstrates the added value of collaboration between laboratories, and across disciplines, to collate and interpret information from clinical testing laboratories to consolidate patient management. ..
  44. Mackereth C, Madl T, Bonnal S, Simon B, Zanier K, Gasch A, et al. Multi-domain conformational selection underlies pre-mRNA splicing regulation by U2AF. Nature. 2011;475:408-11 pubmed publisher
    ..Similar mechanisms of cooperative multi-domain conformational selection may operate more generally in the recognition of degenerate nucleotide or amino acid motifs by multi-domain proteins. ..
  45. Siegel T, Hekstra D, Wang X, Dewell S, Cross G. Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites. Nucleic Acids Res. 2010;38:4946-57 pubmed publisher
    ..Our study demonstrates the usefulness of the RNA-seq technology to study the transcriptional landscape of an organism whose genome has not been fully annotated. ..
  46. Heyd F, Lynch K. Degrade, move, regroup: signaling control of splicing proteins. Trends Biochem Sci. 2011;36:397-404 pubmed publisher
    ..These include regulated synthesis or degradation of splicing factors, differential protein-protein interactions, altered nuclear translocation and changes in transcription elongation...
  47. Mayas R, Maita H, Semlow D, Staley J. Spliceosome discards intermediates via the DEAH box ATPase Prp43p. Proc Natl Acad Sci U S A. 2010;107:10020-5 pubmed publisher
    ..Because Prp43p also promotes spliceosome disassembly after exon ligation, this work establishes a parallel between the discard of suboptimal intermediates and the dissociation of a genuine excised intron product. ..
  48. Lehmann J, Eisenhardt C, Stadler P, Krauss V. Some novel intron positions in conserved Drosophila genes are caused by intron sliding or tandem duplication. BMC Evol Biol. 2010;10:156 pubmed publisher
    ..Intron migration and exon duplication together may account for a significant amount of novel intron positions in conserved coding sequences. ..
  49. Somberg M, Schwartz S. Multiple ASF/SF2 sites in the human papillomavirus type 16 (HPV-16) E4-coding region promote splicing to the most commonly used 3'-splice site on the HPV-16 genome. J Virol. 2010;84:8219-30 pubmed publisher
    ..High levels of ASF/SF2 may therefore be a requirement for progression to cervical cancer. This is supported by our earlier findings that ASF/SF2 is overexpressed in high-grade cervical lesions and cervical cancer. ..
  50. Depienne C, Trouillard O, Gourfinkel An I, Saint Martin C, Bouteiller D, Graber D, et al. Mechanisms for variable expressivity of inherited SCN1A mutations causing Dravet syndrome. J Med Genet. 2010;47:404-10 pubmed publisher
    ..In this latter case, additional genetic or environmental factors likely modulate the severity of the expression of the mutation. ..
  51. Choi J. Contrasting chromatin organization of CpG islands and exons in the human genome. Genome Biol. 2010;11:R70 pubmed publisher
    ..Exonic DNA methylation seems to function together with exonic nucleosomes and H3K36me3 for the proper splicing of transcripts with different expression levels. ..
  52. Gilissen C, Arts H, Hoischen A, Spruijt L, Mans D, Arts P, et al. Exome sequencing identifies WDR35 variants involved in Sensenbrenner syndrome. Am J Hum Genet. 2010;87:418-23 pubmed publisher
    ..WDR35 is homologous to TULP4 (from the Tubby superfamily) and has previously been characterized as an intraflagellar transport component, confirming that Sensenbrenner syndrome is a ciliary disorder. ..
  53. Kapustin Y, Chan E, Sarkar R, Wong F, Vorechovsky I, Winston R, et al. Cryptic splice sites and split genes. Nucleic Acids Res. 2011;39:5837-44 pubmed publisher
    ..This indicates that non-intronic splicing information had a key role in shaping the split structure of eukaryote genes. ..