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Research Paper

Truncating the spliceosomal ‘rope protein’ Prp45 results in Htz1 dependent phenotypes

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Pages 1-17 | Accepted 24 Apr 2024, Published online: 06 May 2024

References

  • Herzel L, Ottoz DSM, Alpert T, et al. Splicing and transcription touch base: co-transcriptional spliceosome assembly and function. Nat Rev Mol Cell Biol. 2017;18(10):637–650. doi: 10.1038/nrm.2017.63
  • Bentley DL. Coupling mRNA processing with transcription in time and space. Nat Rev Genet. 2014;15(3):163–175. doi: 10.1038/nrg3662
  • Luco RF, Allo M, Schor IE, et al. Epigenetics in alternative pre-mRNA splicing. Cell. 2011;144(1):16–26. doi: 10.1016/j.cell.2010.11.056
  • Costanzo M, VanderSluis B, Koch EN, et al. A global genetic interaction network maps a wiring diagram of cellular function. Science. 2016;353(6306):aaf1420–aaf 1420. doi: 10.1126/science.aaf1420
  • Carrillo Oesterreich F, Preibisch S, Neugebauer KM. Global analysis of nascent RNA reveals transcriptional pausing in terminal exons. Mol Cell. 2010;40(4):571–581. doi: 10.1016/j.molcel.2010.11.004
  • Carrillo Oesterreich F, Herzel L, Straube K, et al. Splicing of nascent RNA coincides with intron exit from RNA polymerase II. Cell. 2016;165(2):372–381. doi: 10.1016/j.cell.2016.02.045
  • Khodor YL, Rodriguez J, Abruzzi KC, et al. Nascent-seq indicates widespread cotranscriptional pre-mRNA splicing in Drosophila. Genes Dev. 2011;25(23):2502–2512. doi: 10.1101/gad.178962.111
  • Nojima T, Rebelo K, Gomes T, et al. RNA polymerase II phosphorylated on CTD serine 5 interacts with the spliceosome during Co-transcriptional Splicing. Mol Cell. 2018;72(2):369–379.e4. doi: 10.1016/j.molcel.2018.09.004
  • Milligan L, Sayou C, Tuck A, et al. RNA polymerase II stalling at pre-mRNA splice sites is enforced by ubiquitination of the catalytic subunit. Elife. 2017;6:e27082. doi: 10.7554/eLife.27082
  • Aslanzadeh V, Huang Y, Sanguinetti G, et al. Transcription rate strongly affects splicing fidelity and cotranscriptionality in budding yeast. Genome Res. 2018;28(2):203–213. doi: 10.1101/gr.225615.117
  • Carrocci TJ, Neugebauer KM. Pre-mRNA splicing in the nuclear landscape. Cold Spring Harb Symp Quant Biol. 2019;84:11–20. doi: 10.1101/sqb.2019.84.040402
  • Fica SM. Cryo-EM snapshots of the human spliceosome reveal structural adaptions for splicing regulation. Curr Opin Struct Biol. 2020;65:139–148. doi: 10.1016/j.sbi.2020.06.018
  • Moehle EA, Ryan CJ, Krogan NJ, et al. The yeast SR-Like protein Npl3 links chromatin modification to mRNA processing. Buratowski S, editor. PLOS Genet. 2012;8(11):e1003101. doi: 10.1371/journal.pgen.1003101
  • Minocha R, Popova V, Kopytova D, et al. Mud2 functions in transcription by recruiting the Prp19 and TREX complexes to transcribed genes. Nucleic Acids Res. 2018;46(18):9749–9763. doi: 10.1093/nar/gky640
  • Cech TR. RNA in biological condensates. RNA. 2022;28(1):1–2. doi: 10.1261/rna.079051.121
  • Gunderson FQ, Merkhofer EC, Johnson TL. Dynamic histone acetylation is critical for cotranscriptional spliceosome assembly and spliceosomal rearrangements. Proc Natl Acad Sci. 2011;108(5):2004–2009. doi: 10.1073/pnas.1011982108
  • Hérissant L, Moehle EA, Bertaccini D, et al. H2B ubiquitylation modulates spliceosome assembly and function in budding yeast: histone marks and mRNA splicing. Biol Cell. 2014;106(4):126–138. doi: 10.1111/boc.201400003
  • Sorenson MR, Jha DK, Ucles SA, et al. Histone H3K36 methylation regulates pre-mRNA splicing in Saccharomyces cerevisiae. RNA Biol. 2016;13(4):412–426. doi: 10.1080/15476286.2016.1144009
  • Leung CS, Douglass SM, Morselli M, et al. H3K36 methylation and the chromodomain protein Eaf3 are required for proper cotranscriptional spliceosome assembly. Cell Rep. 2019;27(13):3760–3769.e4. doi: 10.1016/j.celrep.2019.05.100
  • Shao W, Ding Z, Zheng Z-Z, et al. Prp5−Spt8/Spt3 interaction mediates a reciprocal coupling between splicing and transcription. Nucleic Acids Res. 2020;48(11):5799–5813. doi: 10.1093/nar/gkaa311
  • Maudlin IE, Beggs JD. Spt5 modulates cotranscriptional spliceosome assembly in Saccharomyces cerevisiae. RNA. 2019;25(10):1298–1310. doi: 10.1261/rna.070425.119
  • Martinkova K, Lebduska P, Skruzny M, et al. Functional mapping of Saccharomyces cerevisiae Prp45 identifies the SNW domain as essential for viability. J Biochem (Tokyo). 2002;132(4):557–563. doi: 10.1093/oxfordjournals.jbchem.a003257
  • Lenstra TL, Benschop JJ, Kim T, et al. The specificity and topology of chromatin interaction pathways in yeast. Mol Cell. 2011;42(4):536–549. doi: 10.1016/j.molcel.2011.03.026
  • Görnemann J, Kotovic KM, Hujer K, et al. Cotranscriptional spliceosome assembly occurs in a stepwise fashion and requires the cap binding complex. Mol Cell. 2005;19(1):53–63. doi: 10.1016/j.molcel.2005.05.007
  • Haque N, Oberdoerffer S. Chromatin and splicing. Methods Mol Biol Clifton NJ. 2014;1126:97–113.
  • Hnisz D, Shrinivas K, Young RA, et al. A phase separation model for transcriptional control. Cell. 2017;169(1):13–23. doi: 10.1016/j.cell.2017.02.007
  • Henninger JE, Oksuz O, Shrinivas K, et al. RNA-Mediated feedback control of transcriptional condensates. Cell. 2021;184(1):207–225.e24. doi: 10.1016/j.cell.2020.11.030
  • Bhat P, Honson D, Guttman M. Nuclear compartmentalization as a mechanism of quantitative control of gene expression. Nat Rev Mol Cell Biol. 2021;22(10):653–670. doi: 10.1038/s41580-021-00387-1
  • Moehle EA, Braberg H, Krogan NJ, et al. Adventures in time and space: splicing efficiency and RNA polymerase II elongation rate. RNA Biol. 2014;11(4):313–319. doi: 10.4161/rna.28646
  • Aslanzadeh V, Beggs JD. Revisiting the window of opportunity for cotranscriptional splicing in budding yeast. RNA. 2020;26(9):1081–1085. doi: 10.1261/rna.075895.120
  • Chathoth KT, Barrass JD, Webb S, et al. A splicing-dependent transcriptional checkpoint associated with prespliceosome formation. Mol Cell. 2014;53(5):779–790. doi: 10.1016/j.molcel.2014.01.017
  • Harlen KM, Trotta KL, Smith EE, et al. Comprehensive RNA polymerase II interactomes reveal distinct and varied roles for each phospho-CTD residue. Cell Rep. 2016;15(10):2147–2158. doi: 10.1016/j.celrep.2016.05.010
  • Rosonina E, Yurko N, Li W, et al. Threonine-4 of the budding yeast RNAP II CTD couples transcription with Htz1-mediated chromatin remodeling. Proc Natl Acad Sci. 2014;111(33):11924–11931. doi: 10.1073/pnas.1412802111
  • Lu H, Yu D, Hansen AS, et al. Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II. Nature. 2018;558(7709):318–323. doi: 10.1038/s41586-018-0174-3
  • Maita H, Nakagawa S. What is the switch for coupling transcription and splicing? RNA polymerase II C-terminal domain phosphorylation, phase separation and beyond. Wiley Interdiscip Rev RNA. 2020;11(1):e1574. doi: 10.1002/wrna.1574
  • Guo YE, Manteiga JC, Henninger JE, et al. Pol II phosphorylation regulates a switch between transcriptional and splicing condensates. Nature. 2019;572(7770):543–548. doi: 10.1038/s41586-019-1464-0
  • Church MC, Fleming AB. A role for histone acetylation in regulating transcription elongation. Transcription. 2018;9(4):225–232. doi: 10.1080/21541264.2017.1394423
  • Cohen E, Zafrir Z, Tuller T. A code for transcription elongation speed. RNA Biol. 2018;15(1):81–94. doi: 10.1080/15476286.2017.1384118
  • Rahhal R, Seto E. Emerging roles of histone modifications and HDACs in RNA splicing. Nucleic Acids Res. 2019;47(10):4911–4926. doi: 10.1093/nar/gkz292
  • Guillemette B, Gaudreau L. Reuniting the contrasting functions of H2A.Z. This paper is one of a selection of papers published in this special issue, entitled 27th international west coast chromatin and chromosome conference, and has undergone the Journal’s usual peer review process. Biochem Cell Biol Biochim Biol Cell. 2006;84(4):528–535. doi: 10.1139/o06-077
  • Billon P, Côté J. Precise deposition of histone H2A.Z in chromatin for genome expression and maintenance. Biochim Biophys Acta Gene Regul Mech. 2012;1819(3–4):290–302. doi: 10.1016/j.bbagrm.2011.10.004
  • Brewis HT, Wang AY, Gaub A, et al. What makes a histone variant a variant: changing H2A to become H2A.Z. Schneider R, editor. PLOS Genet. 2021;17(12):e1009950. doi: 10.1371/journal.pgen.1009950
  • Sims RJ, Millhouse S, Chen C-F, et al. Recognition of trimethylated histone H3 lysine 4 facilitates the recruitment of transcription postinitiation factors and pre-mRNA splicing. Mol Cell. 2007;28(4):665–676. doi: 10.1016/j.molcel.2007.11.010
  • Fong N, Saldi T, Sheridan RM, et al. RNA Pol II dynamics modulate co-transcriptional chromatin modification, CTD phosphorylation, and transcriptional direction. Mol Cell. 2017;66(4):546–557.e3. doi: 10.1016/j.molcel.2017.04.016
  • Patrick KL, Ryan CJ, Xu J, et al. Genetic interaction mapping reveals a role for the SWI/SNF nucleosome remodeler in spliceosome activation in fission yeast. Bentley D, editor. PLOS Genet. 2015;11(3):e1005074. doi: 10.1371/journal.pgen.1005074
  • Nissen KE, Homer CM, Ryan CJ, et al. The histone variant H2A. Z promotes splicing of weak introns. Genes Dev. 2017;31(7):688–701. doi: 10.1101/gad.295287.116
  • Neves LT, Douglass S, Spreafico R, et al. The histone variant H2A.Z promotes efficient cotranscriptional splicing in S. cerevisiae. Genes Dev. 2017;31(7):702–717. doi: 10.1101/gad.295188.116
  • Bai R, Yan C, Wan R, et al. Structure of the post-catalytic spliceosome from Saccharomyces cerevisiae. Cell. 2017;171(7):1589–1598.e8. doi: 10.1016/j.cell.2017.10.038
  • Jumper J, Evans R, Pritzel A, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596(7873):583–589. doi: 10.1038/s41586-021-03819-2
  • Ruff KM, Pappu RV. AlphaFold and implications for intrinsically disordered proteins. J Mol Biol. 2021;433(20):167208. doi: 10.1016/j.jmb.2021.167208
  • Wan R, Bai R, Yan C, et al. Structures of the catalytically activated yeast spliceosome reveal the mechanism of branching. Cell. 2019;177(2):339–351.e13. doi: 10.1016/j.cell.2019.02.006
  • Albers M, Diment A, Muraru M. Identification and characterization of Prp45p and Prp46p, essential pre-mRNA splicing factors. RNA. 2003;9(1):138–150. doi: 10.1261/rna.2119903
  • Wan R, Bai R, Zhan X, et al. How is precursor messenger RNA spliced by the spliceosome? Annu Rev Biochem. 2020;89(1):333–358. doi: 10.1146/annurev-biochem-013118-111024
  • Yan C, Wan R, Bai R, et al. Structure of a yeast step II catalytically activated spliceosome. Science. 2017;355(6321):149–155. doi: 10.1126/science.aak9979
  • Plaschka C, Newman AJ, Nagai K. Structural basis of nuclear pre-mRNA splicing: lessons from yeast. Cold Spring Harb Perspect Biol. 2019;11(5):a032391. doi: 10.1101/cshperspect.a032391
  • Wilkinson ME, Fica SM, Galej WP, et al. Postcatalytic spliceosome structure reveals mechanism of 3′–splice site selection. Science. 2017;358(6368):1283–1288. doi: 10.1126/science.aar3729
  • Wan R, Yan C, Bai R, et al. Structure of an intron lariat spliceosome from Saccharomyces cerevisiae. Cell. 2017;171(1):120–132.e12. doi: 10.1016/j.cell.2017.08.029
  • Gahura O, Abrhámová K, Skružný M, et al. Prp45 affects Prp22 partition in spliceosomal complexes and splicing efficiency of non-consensus substrates. J Cell Biochem. 2009;106(1):139–151. doi: 10.1002/jcb.21989
  • Harmon TS, Holehouse AS, Rosen MK, et al. Intrinsically disordered linkers determine the interplay between phase separation and gelation in multivalent proteins. Elife. 2017;6:e30294. doi: 10.7554/eLife.30294
  • Zhang C, Baudino TA, Dowd DR, et al. Ternary complexes and cooperative interplay between NCoA-62/Ski-interacting protein and steroid receptor coactivators in vitamin D receptor-mediated transcription. J Biol Chem. 2001;276(44):40614–40620. doi: 10.1074/jbc.M106263200
  • Prathapam T, Kühne C, Banks L. Skip interacts with the retinoblastoma tumor suppressor and inhibits its transcriptional repression activity. Nucleic Acids Res. 2002;30(23):5261–5268. doi: 10.1093/nar/gkf658
  • Brès V, Gomes N, Pickle L, et al. A human splicing factor, SKIP, associates with P-TEFb and enhances transcription elongation by HIV-1 Tat. Genes Dev. 2005;19(10):1211–1226. doi: 10.1101/gad.1291705
  • Chen Y, Zhang L, Jones KA. SKIP counteracts p53-mediated apoptosis via selective regulation of p21Cip1 mRNA splicing. Genes Dev. 2011;25(7):701–716. doi: 10.1101/gad.2002611
  • Brès V, Yoh SM, Jones KA. The multi-tasking P-TEFb complex. Curr Opin Cell Biol. 2008;20(3):334–340. doi: 10.1016/j.ceb.2008.04.008
  • Újvári A, Luse DS. Newly initiated RNA encounters a factor involved in splicing immediately upon emerging from within RNA polymerase II. J Biol Chem. 2004;279(48):49773–49779. doi: 10.1074/jbc.M409087200
  • Ambrozková M, Půta F, Fuková I, et al. The fission yeast ortholog of the coregulator SKIP interacts with the small subunit of U2AF. Biochem Biophys Res Commun. 2001;284(5):1148–1154. doi: 10.1006/bbrc.2001.5108
  • Hálová M, Gahura O, Převorovský M, et al. Nineteen complex–related factor Prp45 is required for the early stages of cotranscriptional spliceosome assembly. RNA. 2017;23(10):1512–1524. doi: 10.1261/rna.061986.117
  • Clark TA, Sugnet CW, Ares M. Genomewide analysis of mRNA processing in yeast using splicing-specific microarrays. Science. 2002;296(5569):907–910. doi: 10.1126/science.1069415
  • Soutourina J. Transcription regulation by the mediator complex. Nat Rev Mol Cell Biol. 2018;19(4):262–274. doi: 10.1038/nrm.2017.115
  • Van Driessche B, Tafforeau L, Hentges P, et al. Additional vectors for PCR-based gene tagging in Saccharomyces cerevisiae and Schizosaccharomyces pombe using nourseothricin resistance. Yeast Chichester Engl. 2005;22(13):1061–1068. doi: 10.1002/yea.1293
  • Storici F, Lewis LK, Resnick MA. In vivo site-directed mutagenesis using oligonucleotides. Nat Biotechnol. 2001;19(8):773–776. doi: 10.1038/90837
  • Tong AHY, Boone C. Synthetic genetic array analysis in Saccharomyces cerevisiae. Methods Mol Biol Clifton NJ. 2006;313:171–192.
  • Winzeler EA, Shoemaker DD, Astromoff A, et al. Functional characterization of the S. cerevisiae genome by gene deletion and parallel analysis. Science. 1999;285(5429):901–906. doi: 10.1126/science.285.5429.901
  • Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods. 2001;25(4):402–408. doi: 10.1006/meth.2001.1262
  • Převorovský M, Hálová M, Abrhámová K, et al. Workflow for genome-wide determination of pre-mRNA splicing efficiency from yeast RNA-seq data. Biomed Res Int. 2016;2016:1–9. doi: 10.1155/2016/4783841
  • Baryshnikova A. Systematic functional annotation and visualization of biological networks. Cell Syst. 2016;2(6):412–421. doi: 10.1016/j.cels.2016.04.014
  • Persson BL, Lagerstedt JO, Pratt JR, et al. Regulation of phosphate acquisition in Saccharomyces cerevisiae. Curr Genet. 2003;43(4):225–244. doi: 10.1007/s00294-003-0400-9
  • Carvin CD, Kladde MP. Effectors of Lysine 4 methylation of histone H3 in Saccharomyces cerevisiae are negative regulators of PHO5 and GAL1-10. J Biol Chem. 2004;279(32):33057–33062. doi: 10.1074/jbc.M405033200
  • Ellison MA, Lederer AR, Warner MH, et al. The Paf1 complex broadly impacts the transcriptome of Saccharomyces cerevisiae. Genetics. 2019;212(3):711–728. doi: 10.1534/genetics.119.302262
  • Query CC, Konarska MM. Suppression of multiple substrate mutations by spliceosomal prp8 alleles suggests functional correlations with ribosomal ambiguity mutants. Mol Cell. 2004;14(3):343–354. doi: 10.1016/S1097-2765(04)00217-5
  • Konarska MM, Vilardell J, Query CC. Repositioning of the reaction intermediate within the catalytic center of the spliceosome. Mol Cell. 2006;21(4):543–553. doi: 10.1016/j.molcel.2006.01.017
  • Chung NC, Miasojedow B, Startek M, et al. Jaccard/Tanimoto similarity test and estimation methods for biological presence-absence data. BMC Bioinf. 2019;20(S15):644. doi: 10.1186/s12859-019-3118-5
  • Gu M, Naiyachit Y, Wood TJ, et al. H2A.Z marks antisense promoters and has positive effects on antisense transcript levels in budding yeast. BMC Genomics. 2015;16(1):99. doi: 10.1186/s12864-015-1247-4
  • Sorenson MR, Stevens SW. Rapid identification of mRNA processing defects with a novel single-cell yeast reporter. RNA. 2014;20(5):732–745. doi: 10.1261/rna.042663.113
  • Sun M, Schwalb B, Pirkl N, et al. Global analysis of eukaryotic mRNA degradation reveals Xrn1-dependent buffering of transcript levels. Mol Cell. 2013;52(1):52–62. doi: 10.1016/j.molcel.2013.09.010
  • Pettersen EF, Goddard TD, Huang CC, et al. UCSF ChimeraX: structure visualization for researchers, educators, and developers. Protein Sci Publ Protein Soc. 2021;30(1):70–82. doi: 10.1002/pro.3943
  • Dion MF, Kaplan T, Kim M, et al. Dynamics of replication-independent histone turnover in budding yeast. Science. 2007;315(5817):1405–1408. doi: 10.1126/science.1134053
  • Abrhámová K, Nemčko F, Libus J, et al. Introns provide a platform for intergenic regulatory feedback of RPL22 paralogs in yeast. Palazzo AF, editor. PLOS ONE. 2018;13(1):e0190685. doi: 10.1371/journal.pone.0190685
  • Herzel L, Neugebauer KM. Quantification of co-transcriptional splicing from RNA-Seq data. Methods. 2015;85:36–43. doi: 10.1016/j.ymeth.2015.04.024
  • VanderSluis B, Costanzo M, Billmann M, et al. Integrating genetic and protein–protein interaction networks maps a functional wiring diagram of a cell. Curr Opin Microbiol. 2018;45:170–179. doi: 10.1016/j.mib.2018.06.004
  • Yang X, Shen Y, Garre E, et al. Stress granule-defective mutants deregulate stress responsive transcripts. Anderson P, editor. PLOS Genet. 2014;10(11):e1004763. doi: 10.1371/journal.pgen.1004763
  • Tavella TA, Cassiano GC, Costa FTM, et al. Yeast-based high-throughput screens for discovery of kinase inhibitors for neglected diseases. Adv Protein Chem Struct Biol. 2021;124:275–309.
  • Shannon P, Markiel A, Ozier O, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 2003;13(11):2498–2504. doi: 10.1101/gr.1239303
  • Kuras L, Borggrefe T, Kornberg RD. Association of the mediator complex with enhancers of active genes. Proc Natl Acad Sci. 2003;100(24):13887–13891. doi: 10.1073/pnas.2036346100
  • Larschan E, Winston F. The Saccharomyces cerevisiae Srb8-Srb11 complex functions with the SAGA complex during Gal4-activated transcription. Mol Cell Biol. 2005;25(1):114–123. doi: 10.1128/MCB.25.1.114-123.2005
  • Nagai S, Davis RE, Mattei PJ, et al. Chromatin potentiates transcription. Proc Natl Acad Sci. 2017;114(7):1536–1541. doi: 10.1073/pnas.1620312114
  • Munding EM, Shiue L, Katzman S, et al. Competition between pre-mRNAs for the splicing machinery drives global regulation of splicing. Mol Cell. 2013;51(3):338–348. doi: 10.1016/j.molcel.2013.06.012
  • Shore D, Zencir S, Albert B. Transcriptional control of ribosome biogenesis in yeast: links to growth and stress signals. Biochem Soc Trans. 2021;49(4):1589–1599. doi: 10.1042/BST20201136
  • Wilkinson ME, Charenton C, Nagai K. RNA splicing by the spliceosome. Annu Rev Biochem. 2020;89(1):359–388. doi: 10.1146/annurev-biochem-091719-064225
  • Bagchi DN, Battenhouse AM, Park D, et al. The histone variant H2A.Z in yeast is almost exclusively incorporated into the +1 nucleosome in the direction of transcription. Nucleic Acids Res. 2019:gkz1075. doi: 10.1093/nar/gkz1075
  • Iyer VR. The specificity of H2A.Z occupancy in the yeast genome and its relationship to transcription. Curr Genet. 2020;66(5):939–944. doi: 10.1007/s00294-020-01087-7
  • Holstege FCP, Jennings EG, Wyrick JJ, et al. Dissecting the regulatory circuitry of a eukaryotic genome. Cell. 1998;95(5):717–728. doi: 10.1016/S0092-8674(00)81641-4
  • Basehoar AD, Zanton SJ, Pugh BF. Identification and distinct regulation of yeast TATA box-containing genes. Cell. 2004;116(5):699–709. doi: 10.1016/S0092-8674(04)00205-3
  • Van Oss SB, Cucinotta CE, Arndt KM. Emerging insights into the roles of the Paf1 complex in gene regulation. Trends Biochem Sci. 2017;42(10):788–798. doi: 10.1016/j.tibs.2017.08.003
  • Fischl H, Howe FS, Furger A, et al. Paf1 has distinct roles in transcription elongation and differential transcript fate. Mol Cell. 2017;65(4):685–698.e8. doi: 10.1016/j.molcel.2017.01.006
  • Song Y-H, Ahn SH. A Bre1-associated protein, large 1 (Lge1), promotes H2B ubiquitylation during the early stages of transcription elongation. J Biol Chem. 2010;285(4):2361–2367. doi: 10.1074/jbc.M109.039255
  • Venkatasubrahmanyam S, Hwang WW, Meneghini MD, et al. Genome-wide, as opposed to local, antisilencing is mediated redundantly by the euchromatic factors Set1 and H2A. Proc Natl Acad Sci, USA. 2007;104(42):16609–16614. doi: 10.1073/pnas.0700914104
  • Sayou C, Millán-Zambrano G, Santos-Rosa H, et al. RNA binding by histone methyltransferases Set1 and Set2. Mol Cell Biol. 2017;37(14):e00165–17. doi: 10.1128/MCB.00165-17
  • Hang M, Smith MM. Genetic analysis implicates the Set3/Hos2 histone deacetylase in the deposition and remodeling of nucleosomes containing H2A.Z. Genetics. 2011;187(4):1053–1066. doi: 10.1534/genetics.110.125419
  • Krogan NJ, Kim M, Tong A, et al. Methylation of histone H3 by Set2 in Saccharomyces cerevisiae is linked to transcriptional elongation by RNA polymerase II. Mol Cell Biol. 2003;23(12):4207–4218. doi: 10.1128/MCB.23.12.4207-4218.2003
  • Jaiswal D, Turniansky R, Green EM. Choose your own adventure: the role of histone modifications in yeast cell fate. J Mol Biol. 2017;429(13):1946–1957. doi: 10.1016/j.jmb.2016.10.018
  • Larson A, Fair BJ, Pleiss JA. Interconnections between RNA-processing pathways revealed by a sequencing-based genetic screen for pre-mRNA splicing mutants in fission yeast. G3: Genes | Genomes | Genetics. 2016;6(6):1513–1523. doi: 10.1534/g3.116.027508
  • Hwang WW, Venkatasubrahmanyam S, Ianculescu AG, et al. A conserved RING finger protein required for histone H2B monoubiquitination and cell size control. Mol Cell. 2003;11(1):261–266. doi: 10.1016/S1097-2765(02)00826-2
  • Pleiss JA, Whitworth GB, Bergkessel M, et al. Transcript specificity in yeast pre-mRNA splicing revealed by mutations in core spliceosomal components. Black DL, editor. PLOS Biol. 2007;5(4):e90. doi: 10.1371/journal.pbio.0050090
  • Brown T, Howe FS, Murray SC, et al. Antisense transcription-dependent chromatin signature modulates sense transcript dynamics. Mol Syst Biol. 2018;14(2):e8007. doi: 10.15252/msb.20178007
  • Zhou Y, Johansson MJO. The pre-mRNA retention and splicing complex controls expression of the mediator subunit Med20. RNA Biol. 2017;14(10):1411–1417. doi: 10.1080/15476286.2017.1294310
  • Bao P, Will CL, Urlaub H, et al. The RES complex is required for efficient transformation of the precatalytic B spliceosome into an activated Bact complex. Genes Dev. 2017;31(23–24):2416–2429. doi: 10.1101/gad.308163.117
  • Rauhut R, Fabrizio P, Dybkov O, et al. Molecular architecture of the Saccharomyces cerevisiae activated spliceosome. Science. 2016;353(6306):1399–1405. doi: 10.1126/science.aag1906
  • Zhou Y, Chen C, Johansson MJO. The pre-mRNA retention and splicing complex controls tRNA maturation by promoting TAN1 expression. Nucleic Acids Res. 2013;41(11):5669–5678. doi: 10.1093/nar/gkt269
  • Scherrer FW, Spingola M. A subset of Mer1p-dependent introns requires Bud13p for splicing activation and nuclear retention. RNA. 2006;12(7):1361–1372. doi: 10.1261/rna.2276806
  • Spingola M. Mer1p is a modular splicing factor whose function depends on the conserved U2 snRNP protein Snu17p. Nucleic Acids Res. 2004;32(3):1242–1250. doi: 10.1093/nar/gkh281
  • He Q, Battistella L, Morse RH. Mediator requirement downstream of chromatin remodeling during transcriptional activation of CHA1 in yeast. J Biol Chem. 2008;283(9):5276–5286. doi: 10.1074/jbc.M708266200
  • Cho W-K, Spille J-H, Hecht M, et al. Mediator and RNA polymerase II clusters associate in transcription-dependent condensates. Science. 2018;361(6400):412–415. doi: 10.1126/science.aar4199
  • Mendoza-Ochoa GI, Barrass JD, Maudlin IE, et al. Blocking late stages of splicing quickly limits pre-spliceosome assembly in vivo. RNA Biol. 2019;16(12):1775–1784. doi: 10.1080/15476286.2019.1657788
  • Rutz B. A dual role for BBP/ScSF1 in nuclear pre-mRNA retention and splicing. Embo J. 2000;19(8):1873–1886. doi: 10.1093/emboj/19.8.1873
  • Legrain P, Rosbash M. Some cis- and trans-acting mutants for splicing target pre-mRNA to the cytoplasm. Cell. 1989;57(4):573–583. doi: 10.1016/0092-8674(89)90127-X
  • Baejen C, Torkler P, Gressel S, et al. Transcriptome maps of mRNP biogenesis factors define pre-mRNA recognition. Mol Cell. 2014;55(5):745–757. doi: 10.1016/j.molcel.2014.08.005
  • Björk P, Wieslander L. Integration of mRNP formation and export. Cell Mol Life Sci. 2017;74(16):2875–2897. doi: 10.1007/s00018-017-2503-3
  • Wang K, Yin C, Du X, et al. A U2-snRNP–independent role of SF3b in promoting mRNA export. Proc Natl Acad Sci. 2019;116(16):7837–7846. doi: 10.1073/pnas.1818835116
  • Galy V, Gadal O, Fromont-Racine M, et al. Nuclear retention of unspliced mRNAs in yeast is mediated by perinuclear Mlp1. Cell. 2004;116(1):63–73. doi: 10.1016/S0092-8674(03)01026-2
  • Gardner JM, Smoyer CJ, Stensrud ES, et al. Targeting of the SUN protein Mps3 to the inner nuclear membrane by the histone variant H2A.Z. J Cell Bio. 2011;193(3):489–507. doi: 10.1083/jcb.201011017
  • Bonde MM, Voegeli S, Baudrimont A, et al. Quantification of pre-mRNA escape rate and synergy in splicing. Nucleic Acids Res. 2014;42(20):12847–12860. doi: 10.1093/nar/gku1014
  • de Moura TR, Mozaffari-Jovin S, Szabó CZK, et al. Prp19/Pso4 is an autoinhibited ubiquitin ligase activated by stepwise assembly of three splicing factors. Mol Cell. 2018;69(6):979–992.e6. doi: 10.1016/j.molcel.2018.02.022
  • Chanarat S, Sträßer K. Splicing and beyond: the many faces of the Prp19 complex. Biochim Biophys Acta BBA – Mol Cell Res. 2013;1833:2126–2134. doi: 10.1016/j.bbamcr.2013.05.023
  • Chanarat S, Seizl M, Sträßer K. The Prp19 complex is a novel transcription elongation factor required for TREX occupancy at transcribed genes. Genes Dev. 2011;25(11):1147–1158. doi: 10.1101/gad.623411
  • Kress TL, Krogan NJ, Guthrie C. A single SR-like protein, Npl3, promotes pre-mRNA splicing in budding yeast. Mol Cell. 2008;32(5):727–734. doi: 10.1016/j.molcel.2008.11.013
  • Sayani S, Chanfreau GF. Sequential RNA degradation pathways provide a fail-safe mechanism to limit the accumulation of unspliced transcripts in Saccharomyces cerevisiae. RNA. 2012;18(8):1563–1572. doi: 10.1261/rna.033779.112
  • Xie Y, Ren Y. Mechanisms of nuclear mRNA export: a structural perspective. Traffic. 2019;20(11):829–840. doi: 10.1111/tra.12691
  • Alexander RD, Innocente SA, Barrass JD, et al. Splicing-dependent RNA polymerase pausing in yeast. Mol Cell. 2010;40(4):582–593. doi: 10.1016/j.molcel.2010.11.005
  • Chen H, Pugh BF. What do transcription factors interact with? J Mol Biol. 2021;433(14):166883. doi: 10.1016/j.jmb.2021.166883
  • Huranová M, Ivani I, Benda A, et al. The differential interaction of snRnps with pre-mRNA reveals splicing kinetics in living cells. J Cell Bio. 2010;191(1):75–86. doi: 10.1083/jcb.201004030
  • Neugebauer KM. Nascent RNA and the coordination of splicing with transcription. Cold Spring Harb Perspect Biol. 2019;11(8):a032227. doi: 10.1101/cshperspect.a032227
  • de Coelho Ribeiro ML, Espinosa J, Islam S, et al. Malleable ribonucleoprotein machine: protein intrinsic disorder in the Saccharomyces cerevisiae spliceosome. PeerJ. 2013;1:e2. doi: 10.7717/peerj.2
  • van der Feltz C, Hoskins AA. Structural and functional modularity of the U2 snRNP in pre-mRNA splicing. Crit Rev Biochem Mol Biol. 2019;54(5):443–465. doi: 10.1080/10409238.2019.1691497
  • Harlen KM, Churchman LS. The code and beyond: transcription regulation by the RNA polymerase II carboxy-terminal domain. Nat Rev Mol Cell Biol. 2017;18(4):263–273. doi: 10.1038/nrm.2017.10
  • Lin Y, Protter DSW, Rosen MK, et al. Formation and maturation of phase-separated liquid droplets by RNA-Binding proteins. Mol Cell. 2015;60(2):208–219. doi: 10.1016/j.molcel.2015.08.018
  • Guo Q, Shi X, Wang X. RNA and liquid-liquid phase separation. Non-Coding RNA Res. 2021;6(2):92–99. doi: 10.1016/j.ncrna.2021.04.003
  • Shaban HA, Barth R, Bystricky K. Navigating the crowd: visualizing coordination between genome dynamics, structure, and transcription. Genome Biol. 2020;21(1):278. doi: 10.1186/s13059-020-02185-y
  • Duss O, Stepanyuk GA, Puglisi JD, et al. Transient protein-RNA interactions guide nascent ribosomal RNA folding. Cell. 2019;179(6):1357–1369.e16. doi: 10.1016/j.cell.2019.10.035
  • Rodgers ML, Woodson SA. Transcription increases the cooperativity of ribonucleoprotein assembly. Cell. 2019;179(6):1370–1381.e12. doi: 10.1016/j.cell.2019.11.007
  • Frumkin I, Yofe I, Bar-Ziv R, et al. Evolution of intron splicing towards optimized gene expression is based on various cis- and trans-molecular mechanisms. Hurst LD, editor. PLOS Biol. 2019;17(8):e3000423. doi: 10.1371/journal.pbio.3000423
  • Liao SE, Regev O. Splicing at the phase-separated nuclear speckle interface: a model. Nucleic Acids Res. 2021;49(2):636–645. doi: 10.1093/nar/gkaa1209
  • Gordon JM, Phizicky DV, Neugebauer KM. Nuclear mechanisms of gene expression control: pre-mRNA splicing as a life or death decision. Curr Opin Genet Dev. 2021;67:67–76. doi: 10.1016/j.gde.2020.11.002