spliceosomes

Summary

Summary: Organelles in which the splicing and excision reactions that remove introns from precursor messenger RNA molecules occur. One component of a spliceosome is five small nuclear RNA molecules (U1, U2, U4, U5, U6) that, working in conjunction with proteins, help to fold pieces of RNA into the right shapes and later splice them into the message.

Top Publications

  1. Fabrizio P, Dannenberg J, Dube P, Kastner B, Stark H, Urlaub H, et al. The evolutionarily conserved core design of the catalytic activation step of the yeast spliceosome. Mol Cell. 2009;36:593-608 pubmed publisher
    Metazoan spliceosomes exhibit an elaborate protein composition required for canonical and alternative splicing. Thus, the minimal set of proteins essential for activation and catalysis remains elusive...
  2. Wolf E, Kastner B, Deckert J, Merz C, Stark H, Luhrmann R. Exon, intron and splice site locations in the spliceosomal B complex. EMBO J. 2009;28:2283-92 pubmed publisher
    ..and the 5' and 3' exons of a model pre-mRNA, as well as the U2-associated protein SF3b155, in pre-catalytic spliceosomes (i.e. B complexes) by labelling them with an antibody that bears colloidal gold...
  3. Chanarat S, Seizl M, Strasser K. The Prp19 complex is a novel transcription elongation factor required for TREX occupancy at transcribed genes. Genes Dev. 2011;25:1147-58 pubmed publisher
  4. Clelland A, Bales A, Sleeman J. Changes in intranuclear mobility of mature snRNPs provide a mechanism for splicing defects in spinal muscular atrophy. J Cell Sci. 2012;125:2626-37 pubmed publisher
    ..Thus, alteration of the intranuclear mobility of snRNPs provides a molecular mechanism for splicing defects in SMA...
  5. Coltri P, Effenberger K, Chalkley R, Burlingame A, Jurica M. Breaking up the C complex spliceosome shows stable association of proteins with the lariat intron intermediate. PLoS ONE. 2011;6:e19061 pubmed publisher
    ..The results also suggest a set of candidate proteins that hold the lariat-intron intermediate together in C complex. This information is critical for further interpreting the complex architecture of the mammalian spliceosome...
  6. Roy S, Irimia M. Genome evolution: where do new introns come from?. Curr Biol. 2012;22:R529-31 pubmed publisher
    ..Resonances to a case in unrelated algae suggest such elements hold general answers to long-standing mysteries of intron evolution...
  7. Palfi Z, Jaé N, Preusser C, Kaminska K, Bujnicki J, Lee J, et al. SMN-assisted assembly of snRNP-specific Sm cores in trypanosomes. Genes Dev. 2009;23:1650-64 pubmed publisher
    ..These data establish a novel role of SMN, mediating snRNP specificity in Sm core assembly, and yield new biochemical insight into the mechanism of SMN activity...
  8. Anokhina M, Bessonov S, Miao Z, Westhof E, Hartmuth K, Luhrmann R. RNA structure analysis of human spliceosomes reveals a compact 3D arrangement of snRNAs at the catalytic core. EMBO J. 2013;32:2804-18 pubmed publisher
    ..roles in splicing, little is known about the 3D arrangement of U2, U6, and U5 snRNAs and the pre-mRNA in active spliceosomes. To elucidate their relative spatial organization and dynamic rearrangement, we examined the RNA structure of ..
  9. Wong A, Zhang S, Mordue D, Wu J, Zhang Z, Darzynkiewicz Z, et al. PDIP38 is translocated to the spliceosomes/nuclear speckles in response to UV-induced DNA damage and is required for UV-induced alternative splicing of MDM2. Cell Cycle. 2013;12:3184-93 pubmed publisher
    ..Using various markers for different nuclear subcompartments, the UV-induced PDIP38 foci were identified as spliceosomes/nuclear speckles, the storage and assembly sites for mRNA splicing factors...

More Information

Publications62

  1. Query C, Konarska M. CEF1/CDC5 alleles modulate transitions between catalytic conformations of the spliceosome. RNA. 2012;18:1001-13 pubmed publisher
  2. Ren L, McLean J, Hazbun T, Fields S, VANDER KOOI C, Ohi M, et al. Systematic two-hybrid and comparative proteomic analyses reveal novel yeast pre-mRNA splicing factors connected to Prp19. PLoS ONE. 2011;6:e16719 pubmed publisher
    ..Our multi-faceted approach has revealed new low abundance splicing factors connected to NTC function, provides evidence for distinct Prp19 containing complexes, and underscores the role of the Prp19 WD40 domain as a splicing scaffold...
  3. Chiou N, Shankarling G, Lynch K. hnRNP L and hnRNP A1 induce extended U1 snRNA interactions with an exon to repress spliceosome assembly. Mol Cell. 2013;49:972-82 pubmed publisher
    ..Together, our results demonstrate that conformational perturbations within the spliceosome are a naturally occurring and generalizable mechanism for controlling alternative splicing decisions...
  4. Pena V, Jovin S, Fabrizio P, Orlowski J, Bujnicki J, Luhrmann R, et al. Common design principles in the spliceosomal RNA helicase Brr2 and in the Hel308 DNA helicase. Mol Cell. 2009;35:454-66 pubmed publisher
  5. Brody Y, Neufeld N, Bieberstein N, Causse S, Böhnlein E, Neugebauer K, et al. The in vivo kinetics of RNA polymerase II elongation during co-transcriptional splicing. PLoS Biol. 2011;9:e1000573 pubmed publisher
    ..This indicates that nascent RNA can assemble multiple spliceosomes simultaneously...
  6. Kim W, Jung H, Kwak K, Kim M, Oh S, Han Y, et al. The Arabidopsis U12-type spliceosomal protein U11/U12-31K is involved in U12 intron splicing via RNA chaperone activity and affects plant development. Plant Cell. 2010;22:3951-62 pubmed publisher
    ..Importantly, U11/U12-31K was determined to harbor RNA chaperone activity. We propose that U11/U12-31K is an RNA chaperone that is indispensible for proper U12 intron splicing and for normal growth and development of plants...
  7. Farlow A, Meduri E, Dolezal M, Hua L, Schlotterer C. Nonsense-mediated decay enables intron gain in Drosophila. PLoS Genet. 2010;6:e1000819 pubmed publisher
    ..This mechanism reduces the sequence requirement imposed on novel introns and implies that the capacity of the spliceosome to recognize weak splice sites was a prerequisite for intron gain during eukaryotic evolution...
  8. Boulisfane N, Choleza M, Rage F, Neel H, Soret J, Bordonné R. Impaired minor tri-snRNP assembly generates differential splicing defects of U12-type introns in lymphoblasts derived from a type I SMA patient. Hum Mol Genet. 2011;20:641-8 pubmed publisher
    ..Our results suggest that SMA might result from the inefficient splicing of one or only a few pre-mRNAs carrying minor introns and coding for proteins required for motor neurons function and/or organization...
  9. Vesteg M, Sándorová Z, Krajcovic J. Selective forces for the origin of spliceosomes. J Mol Evol. 2012;74:226-31 pubmed publisher
    It has been proposed that eukaryotic spliceosomes evolved from bacterial group II introns via constructive neutral changes...
  10. Kumar P, Kumar P, Lindberg L, Thirkill T, Ji J, Martsching L, et al. The MUC1 extracellular domain subunit is found in nuclear speckles and associates with spliceosomes. PLoS ONE. 2012;7:e42712 pubmed publisher
    ..These results suggest that MUC1-N translocates to the nucleus where it is expressed in nuclear speckles and that MUC1-N and MUC1-C have dissimilar intranuclear distribution patterns...
  11. van der Feltz C, Anthony K, Brilot A, Pomeranz Krummel D. Architecture of the spliceosome. Biochemistry. 2012;51:3321-33 pubmed publisher
    ..This review provides an overview of our current understanding of the architecture of the spliceosome and the RNA-protein complexes integral to its function, the U snRNPs...
  12. Gao X, Zhao X, Zhu Y, He J, Shao J, Su C, et al. Tudor staphylococcal nuclease (Tudor-SN) participates in small ribonucleoprotein (snRNP) assembly via interacting with symmetrically dimethylated Sm proteins. J Biol Chem. 2012;287:18130-41 pubmed publisher
    ..Our results reveal the molecular basis for the involvement of Tudor-SN in regulating small nuclear ribonucleoprotein biogenesis, which provides novel insight related to the biological activity of Tudor-SN...
  13. Huranová M, Ivani I, Benda A, Poser I, Brody Y, Hof M, et al. The differential interaction of snRNPs with pre-mRNA reveals splicing kinetics in living cells. J Cell Biol. 2010;191:75-86 pubmed publisher
    ..These results are consistent with the predictions of the step-wise model of spliceosome assembly and provide an estimate on the rate of splicing in human cells...
  14. Leung A, Kambach C, Kondo Y, Kampmann M, Jinek M, Nagai K. Use of RNA tertiary interaction modules for the crystallisation of the spliceosomal snRNP core domain. J Mol Biol. 2010;402:154-64 pubmed publisher
    ..Here, we describe various strategies employed in our crystallisation effort that could be applied to crystallisation of other RNP particles...
  15. Kosowski T, Keys H, Quan T, Ruby S. DExD/H-box Prp5 protein is in the spliceosome during most of the splicing cycle. RNA. 2009;15:1345-62 pubmed publisher
    ..It cosediments with active spliceosomes isolated by glycerol gradient centrifugation...
  16. Kudla G, Granneman S, Hahn D, Beggs J, Tollervey D. Cross-linking, ligation, and sequencing of hybrids reveals RNA-RNA interactions in yeast. Proc Natl Acad Sci U S A. 2011;108:10010-5 pubmed publisher
    ..CLASH should allow transcriptome-wide analyses of RNA-RNA interactions in many organisms...
  17. Hernandez H, Makarova O, Makarov E, Morgner N, Muto Y, Krummel D, et al. Isoforms of U1-70k control subunit dynamics in the human spliceosomal U1 snRNP. PLoS ONE. 2009;4:e7202 pubmed publisher
    ..These results therefore provide the important functional link between proteomics and structure as well as insight into the dynamic quaternary structure of the native U1 snRNP important for its function...
  18. Kuroyanagi H. Fox-1 family of RNA-binding proteins. Cell Mol Life Sci. 2009;66:3895-907 pubmed publisher
    ..Further systematic elucidation of target genes of the Fox-1 family and other splicing regulators in various tissues will lead to a comprehensive understanding of splicing regulatory networks...
  19. Makishima H, Visconte V, Sakaguchi H, Jankowska A, Abu Kar S, Jerez A, et al. Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis. Blood. 2012;119:3203-10 pubmed publisher
    ..Spliceosomal genes are probably tumor suppressors, and their mutations may constitute diagnostic biomarkers that could potentially serve as therapeutic targets...
  20. Rossi D, Bruscaggin A, Spina V, Rasi S, Khiabanian H, Messina M, et al. Mutations of the SF3B1 splicing factor in chronic lymphocytic leukemia: association with progression and fludarabine-refractoriness. Blood. 2011;118:6904-8 pubmed publisher
    ..046). The identification of SF3B1 mutations points to splicing regulation as a novel pathogenetic mechanism of potential clinical relevance in CLL...
  21. Cordin O, Beggs J. RNA helicases in splicing. RNA Biol. 2013;10:83-95 pubmed publisher
    ..This review focuses on recent advances in the characterization of the splicing helicases and their interactions, and highlights the deep integration of splicing helicases in global mRNP biogenesis pathways...
  22. Ilagan J, Chalkley R, Burlingame A, Jurica M. Rearrangements within human spliceosomes captured after exon ligation. RNA. 2013;19:400-12 pubmed publisher
    In spliceosomes, dynamic RNA/RNA and RNA/protein interactions position the pre-mRNA substrate for the two chemical steps of splicing...
  23. Galej W, Oubridge C, Newman A, Nagai K. Crystal structure of Prp8 reveals active site cavity of the spliceosome. Nature. 2013;493:638-43 pubmed publisher
    ..The structure provides crucial insights into the architecture of the spliceosome active site, and reinforces the notion that nuclear pre-mRNA splicing and group?II intron splicing have a common origin...
  24. Catania F, Gao X, Scofield D. Endogenous mechanisms for the origins of spliceosomal introns. J Hered. 2009;100:591-6 pubmed publisher
    ..These two nonmutually exclusive hypotheses provide a powerful way to explain the establishment of spliceosomal introns in eukaryotes without invoking an exogenous source...
  25. Kamikawa R, Inagaki Y, Tokoro M, Roger A, Hashimoto T. Split introns in the genome of Giardia intestinalis are excised by spliceosome-mediated trans-splicing. Curr Biol. 2011;21:311-5 pubmed publisher
    ..The divergent unicellular eukaryote Giardia intestinalis, the causative agent of giardiasis, also possesses spliceosomes, but only four canonical (cis-spliced) introns have been identified in its genome to date...
  26. Valadkhan S, Jaladat Y. The spliceosomal proteome: at the heart of the largest cellular ribonucleoprotein machine. Proteomics. 2010;10:4128-41 pubmed publisher
  27. Edery P, Marcaillou C, Sahbatou M, Labalme A, Chastang J, Touraine R, et al. Association of TALS developmental disorder with defect in minor splicing component U4atac snRNA. Science. 2011;332:240-3 pubmed publisher
    ..Our findings demonstrate a crucial role of the minor spliceosome component U4atac snRNA in early human development and postnatal survival...
  28. Karijolich J, Yu Y. Spliceosomal snRNA modifications and their function. RNA Biol. 2010;7:192-204 pubmed
    ..The role of spliceosomal snRNA modifications in snRNP biogenesis and spliceosome assembly has also been verified...
  29. Ohrt T, Odenwälder P, Dannenberg J, Prior M, Warkocki Z, Schmitzová J, et al. Molecular dissection of step 2 catalysis of yeast pre-mRNA splicing investigated in a purified system. RNA. 2013;19:902-15 pubmed publisher
    ..Our results shed new light on the factor requirements for step 2 catalysis and the dynamics of step 1 and 2 factors during the catalytic steps of splicing...
  30. Sebbag Sznajder N, Raitskin O, Angenitzki M, Sato T, Sperling J, Sperling R. Regulation of alternative splicing within the supraspliceosome. J Struct Biol. 2012;177:152-9 pubmed publisher
    ..These observations support the proposed role of the supraspliceosome in splicing regulation and alternative splicing...
  31. Hegele A, Kamburov A, Grossmann A, Sourlis C, Wowro S, Weimann M, et al. Dynamic protein-protein interaction wiring of the human spliceosome. Mol Cell. 2012;45:567-80 pubmed publisher
    More than 200 proteins copurify with spliceosomes, the compositionally dynamic RNPs catalyzing pre-mRNA splicing...
  32. Dlakic M, Mushegian A. Prp8, the pivotal protein of the spliceosomal catalytic center, evolved from a retroelement-encoded reverse transcriptase. RNA. 2011;17:799-808 pubmed publisher
    ..This is only the second example-the other one being telomerase-of the RT recruitment from a genomic parasite to serve an essential cellular function...
  33. Koonin E. Intron-dominated genomes of early ancestors of eukaryotes. J Hered. 2009;100:618-23 pubmed publisher
    ..An organism with such an unusual genome architecture could survive only under conditions of a severe population bottleneck...
  34. Agafonov D, Deckert J, Wolf E, Odenwälder P, Bessonov S, Will C, et al. Semiquantitative proteomic analysis of the human spliceosome via a novel two-dimensional gel electrophoresis method. Mol Cell Biol. 2011;31:2667-82 pubmed publisher
    More than 200 proteins associate with human spliceosomes, but little is known about their relative abundances in a given spliceosomal complex...
  35. Tanackovic G, Ransijn A, Thibault P, Abou Elela S, Klinck R, Berson E, et al. PRPF mutations are associated with generalized defects in spliceosome formation and pre-mRNA splicing in patients with retinitis pigmentosa. Hum Mol Genet. 2011;20:2116-30 pubmed publisher
    ..Although these mutations cause widespread and important splicing defects, they are likely tolerated by the majority of human tissues but are critical for retinal cell survival...
  36. Roybal G, Jurica M. Spliceostatin A inhibits spliceosome assembly subsequent to prespliceosome formation. Nucleic Acids Res. 2010;38:6664-72 pubmed publisher
    ..in addition to its established function in early U2 snRNP recruitment, SF3b plays a role in later maturation of spliceosomes. This work establishes SSA as a powerful tool for dissecting the dynamics of spliceosomes in cells...
  37. 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...
  38. Ragg H, Kumar A, Köster K, Bentele C, Wang Y, Frese M, et al. Multiple gains of spliceosomal introns in a superfamily of vertebrate protease inhibitor genes. BMC Evol Biol. 2009;9:208 pubmed publisher
    ..Previous investigations have shown that, during metazoan radiation, the exon-intron patterns of serpin superfamily genes were subject to massive changes, in contrast to many other genes...
  39. Chiu Y, Liu Y, Chiang T, Yeh T, Tseng C, Wu N, et al. Cwc25 is a novel splicing factor required after Prp2 and Yju2 to facilitate the first catalytic reaction. Mol Cell Biol. 2009;29:5671-8 pubmed publisher
    ..These results have implications for the possible roles of Cwc25 and HP-X in facilitating juxtaposition of the 5' splice site and the branch point during the first catalytic reaction...
  40. Song E, Werner S, Neubauer J, Stegmeier F, Aspden J, Rio D, et al. The Prp19 complex and the Usp4Sart3 deubiquitinating enzyme control reversible ubiquitination at the spliceosome. Genes Dev. 2010;24:1434-47 pubmed publisher
    ..We propose that the reversible ubiquitination of spliceosomal proteins, such as Prp3, guides rearrangements in the composition of the spliceosome at distinct steps of the splicing reaction...
  41. van der Burgt A, Severing E, de Wit P, Collemare J. Birth of new spliceosomal introns in fungi by multiplication of introner-like elements. Curr Biol. 2012;22:1260-5 pubmed publisher
    ..We suggest that ILEs not only account for intron gains in six fungi but also in ancestral eukaryotes to give rise to most RSIs by a yet unknown multiplication mechanism...
  42. Ohrt T, Prior M, Dannenberg J, Odenwälder P, Dybkov O, Rasche N, et al. Prp2-mediated protein rearrangements at the catalytic core of the spliceosome as revealed by dcFCCS. RNA. 2012;18:1244-56 pubmed publisher
    ..of several proteins is significantly changed during the Prp2-mediated transition of precatalytic B(act) spliceosomes to catalytically activated B* spliceosomes from Saccharomyces cerevisiae...
  43. Gunderson F, Merkhofer E, Johnson T. Dynamic histone acetylation is critical for cotranscriptional spliceosome assembly and spliceosomal rearrangements. Proc Natl Acad Sci U S A. 2011;108:2004-9 pubmed publisher
    ..These studies show that cotranscriptional spliceosome rearrangements are driven by dynamic changes in the acetylation state of histones and provide a model whereby yeast spliceosome assembly is tightly coupled to histone modification...
  44. Saha D, Khandelia P, O Keefe R, Vijayraghavan U. Saccharomyces cerevisiae NineTeen complex (NTC)-associated factor Bud31/Ycr063w assembles on precatalytic spliceosomes and improves first and second step pre-mRNA splicing efficiency. J Biol Chem. 2012;287:5390-9 pubmed publisher
    Pre-mRNA splicing occurs in spliceosomes whose assembly and activation are critical for splice site selection and catalysis...
  45. Korneta I, Magnus M, Bujnicki J. Structural bioinformatics of the human spliceosomal proteome. Nucleic Acids Res. 2012;40:7046-65 pubmed publisher
    ..The results of this work will aid experimental and structural analyses of the spliceosomal proteins and complexes, and can serve as a starting point for multiscale modeling of the structure of the entire spliceosome...
  46. Yeh T, Liu H, Chung C, Wu N, Liu Y, Cheng S. Splicing factor Cwc22 is required for the function of Prp2 and for the spliceosome to escape from a futile pathway. Mol Cell Biol. 2011;31:43-53 pubmed publisher
    ..Thus, Cwc22 represents a novel ATP-dependent step one factor besides Prp2 and Spp2 and has a distinct role from that of Spp2 in mediating the function of Prp2...
  47. Tseng C, Liu H, Cheng S. DEAH-box ATPase Prp16 has dual roles in remodeling of the spliceosome in catalytic steps. RNA. 2011;17:145-54 pubmed publisher
    ..Our results uncovered novel functions of Prp16 in both catalytic steps, and provide mechanistic insights into splicing catalysis...
  48. Valadkhan S. Role of the snRNAs in spliceosomal active site. RNA Biol. 2010;7:345-53 pubmed
    ..Thus, whether the spliceosome is an RNA or RNA-protein catalyst remains uncertain...
  49. Khanna M, van Bakel H, Tang X, Calarco J, Babak T, Guo G, et al. A systematic characterization of Cwc21, the yeast ortholog of the human spliceosomal protein SRm300. RNA. 2009;15:2174-85 pubmed publisher
    ..Together, the results suggest multiple functions for Cwc21/SRm300 in the splicing process, including an important role in the activation of splicing in association with Isy1...
  50. Hoskins A, Friedman L, Gallagher S, Crawford D, Anderson E, Wombacher R, et al. Ordered and dynamic assembly of single spliceosomes. Science. 2011;331:1289-95 pubmed publisher
    ..genetic engineering, chemical biology, and multiwavelength fluorescence microscopy to follow assembly of single spliceosomes in real time in whole-cell extracts...
  51. Cho S, Hoang A, Sinha R, Zhong X, Fu X, Krainer A, et al. Interaction between the RNA binding domains of Ser-Arg splicing factor 1 and U1-70K snRNP protein determines early spliceosome assembly. Proc Natl Acad Sci U S A. 2011;108:8233-8 pubmed publisher
  52. Fica S, Tuttle N, Novak T, Li N, Lu J, Koodathingal P, et al. RNA catalyses nuclear pre-mRNA splicing. Nature. 2013;503:229-34 pubmed publisher
    ..By using metal rescue strategies in spliceosomes from budding yeast, here we show that the U6 snRNA catalyses both of the two splicing reactions by positioning ..
  53. Frazer L, Lovell S, O Keefe R. Analysis of synthetic lethality reveals genetic interactions between the GTPase Snu114p and snRNAs in the catalytic core of the Saccharomyces cerevisiae spliceosome. Genetics. 2009;183:497-515-1SI-4SI pubmed publisher
    ..We propose that the RNA base pairing state is directly or indirectly sensed by the Snu114p G domain allowing the Snu114p C-terminal domain to regulate Brr2p or other proteins to bring about RNA/RNA rearrangements required for splicing...