A Complex Gene Regulatory Mechanism that Operates at the Nexus of Multiple RNA Processing Decisions

Expression of crs1 pre-mRNA, encoding a meiotic cyclin, is blocked in actively growing fission yeast cells by a multifaceted mechanism. The most striking feature is that in vegetative cells, crs1 transcripts are continuously synthesized but are targeted for degradation rather than splicing and polyadenylation. Turnover of crs1 RNA requires the exosome, as do previously described nuclear surveillance and silencing mechanisms, but does not involve a noncanonical poly(A) polymerase. Instead, crs1 transcripts are targeted for destruction by a factor previously implicated in turnover of meiotic RNAs in growing cells. Like exosome mutants, mmi1 mutants splice and polyadenylate vegetative crs1 transcripts. Two regulatory elements are located at the 3′ end of the crs1 gene, consistent with the increased accumulation of spliced RNA in polyadenylation factor mutants. This highly integrated regulatory strategy may ensure a rapid response to adverse conditions, thereby guaranteeing survival.

[1]  M. Yamamoto,et al.  Negative control for the initiation of meiosis in Schizosaccharomyces pombe. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[2]  T. Shenk,et al.  Functional analysis of point mutations in the AAUAAA motif of the SV40 late polyadenylation signal. , 1989, Nucleic acids research.

[3]  K. Maundrell nmt1 of fission yeast. A highly transcribed gene completely repressed by thiamine. , 1990, The Journal of biological chemistry.

[4]  S. Rose,et al.  In vitro polyadenylation is stimulated by the presence of an upstream intron. , 1990, Genes & development.

[5]  M. Goebl,et al.  The fission yeast dis3+ gene encodes a 110-kDa essential protein implicated in mitotic control , 1991, Molecular and cellular biology.

[6]  S. Berget,et al.  Mutation of the AAUAAA polyadenylation signal depresses in vitro splicing of proximal but not distal introns. , 1991, Genes & development.

[7]  S. Moreno,et al.  Molecular genetic analysis of fission yeast Schizosaccharomyces pombe. , 1991, Methods in enzymology.

[8]  K. Maundrell,et al.  TATA box mutations in the Schizosaccharomyces pombe nmt1 promoter affect transcription efficiency but not the transcription start point or thiamine repressibility. , 1993, Gene.

[9]  R. Seong,et al.  Differential expression of the rhp51+ gene, a recA and RAD51 homolog from the fission yeast Schizosaccharomyces pombe. , 1996, Gene.

[10]  P Cramer,et al.  Functional association between promoter structure and transcript alternative splicing. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[11]  N. Proudfoot,et al.  Transcriptional termination signals for RNA polymerase II in fission yeast , 1997, The EMBO journal.

[12]  N. Proudfoot,et al.  Nascent transcription from the nmt1 and nmt2 genes of Schizosaccharomyces pombe overlaps neighbouring genes , 1998, The EMBO journal.

[13]  J. Alwine,et al.  Utilization of Splicing Elements and Polyadenylation Signal Elements in the Coupling of Polyadenylation and Last-Intron Removal , 1999, Molecular and Cellular Biology.

[14]  N. Proudfoot,et al.  Definition of Transcriptional Pause Elements in Fission Yeast , 1999, Molecular and Cellular Biology.

[15]  D. Tollervey,et al.  Identification of a Regulated Pathway for Nuclear Pre-mRNA Turnover , 2000, Cell.

[16]  W. Keller,et al.  The WD‐repeat protein Pfs2p bridges two essential factors within the yeast pre‐mRNA 3′‐end‐processing complex , 2000, The EMBO journal.

[17]  M. Ares,et al.  A yeast intronic splicing enhancer and Nam8p are required for Mer1p-activated splicing. , 2000, Molecular cell.

[18]  J. Manley,et al.  Complex Protein Interactions within the Human Polyadenylation Machinery Identify a Novel Component , 2000, Molecular and Cellular Biology.

[19]  C. Shimoda,et al.  The 5′ terminal region of the Schizosaccharomyces pombe mes1 mRNA is crucial for its meiosis-specific splicing , 2001, Molecular Genetics and Genomics.

[20]  M. Rosbash,et al.  Quality control of mRNA 3′-end processing is linked to the nuclear exosome , 2001, Nature.

[21]  D. Bentley,et al.  Capping, splicing, and 3' processing are independently stimulated by RNA polymerase II: different functions for different segments of the CTD. , 2001, Genes & development.

[22]  H. Nojima,et al.  Comprehensive isolation of meiosis-specific genes identifies novel proteins and unusual non-coding transcripts in Schizosaccharomyces pombe. , 2001, Nucleic acids research.

[23]  K. Tatebayashi,et al.  The dhp1(+) gene, encoding a putative nuclear 5'-->3' exoribonuclease, is required for proper chromosome segregation in fission yeast. , 2001, Nucleic acids research.

[24]  D Gautheret,et al.  Identification of alternate polyadenylation sites and analysis of their tissue distribution using EST data. , 2001, Genome research.

[25]  R. Lyne,et al.  The transcriptional program of meiosis and sporulation in fission yeast , 2002, Nature Genetics.

[26]  J. Lis,et al.  The RNA processing exosome is linked to elongating RNA polymerase II in Drosophila , 2002, Nature.

[27]  Tom Maniatis,et al.  Promoter choice determines splice site selection in protocadherin alpha and gamma pre-mRNA splicing. , 2002, Molecular cell.

[28]  S. Stamm,et al.  YTH: a new domain in nuclear proteins. , 2002, Trends in biochemical sciences.

[29]  Tom Maniatis,et al.  Promoter Choice Determines Splice Site Selection in Protocadherin α and γ Pre-mRNA Splicing , 2002 .

[30]  Subhra Chakraborty,et al.  Premature termination of RNA polymerase II mediated transcription of a seed protein gene in Schizosaccharomyces pombe , 2002, Nucleic Acids Res..

[31]  A. Garzón,et al.  Poly(A) site choice during mRNA 3′-end formation in the Schizosaccharomyces pombe wos2 gene , 2002, Molecular Genetics and Genomics.

[32]  T. Maniatis,et al.  An extensive network of coupling among gene expression machines , 2002, Nature.

[33]  R. Macknight,et al.  Autoregulation of FCA pre‐mRNA processing controls Arabidopsis flowering time , 2003, The EMBO journal.

[34]  N. Krogan,et al.  The yeast Rat1 exonuclease promotes transcription termination by RNA polymerase II , 2004, Nature.

[35]  N. Proudfoot,et al.  Human 5′ → 3′ exonuclease Xrn2 promotes transcription termination at co-transcriptional cleavage sites , 2004, Nature.

[36]  C. Shimoda,et al.  Meiosis-dependent mRNA splicing of the fission yeast Schizosaccharomyces pombe mes1+ gene , 1994, Current Genetics.

[37]  Antonin Morillon,et al.  Gene loops juxtapose promoters and terminators in yeast , 2004, Nature Genetics.

[38]  J. Wilusz,et al.  Bringing the role of mRNA decay in the control of gene expression into focus. , 2004, Trends in genetics : TIG.

[39]  Nick Proudfoot,et al.  New perspectives on connecting messenger RNA 3' end formation to transcription. , 2004, Current opinion in cell biology.

[40]  E. Petfalski,et al.  RNA Degradation by the Exosome Is Promoted by a Nuclear Polyadenylation Complex , 2005, Cell.

[41]  J. Leatherwood,et al.  Negative control contributes to an extensive program of meiotic splicing in fission yeast. , 2005, Molecular cell.

[42]  P. Nurse,et al.  A Meiosis-Specific Cyclin Regulated by Splicing Is Required for Proper Progression through Meiosis , 2005, Molecular and Cellular Biology.

[43]  T. Toda,et al.  Inactivation of the Pre-mRNA Cleavage and Polyadenylation Factor Pfs2 in Fission Yeast Causes Lethal Cell Cycle Defects , 2005, Molecular and Cellular Biology.

[44]  I. Henderson,et al.  An allelic series reveals essential roles for FY in plant development in addition to flowering-time control , 2005, Development.

[45]  A. Kornblihtt,et al.  Promoter usage and alternative splicing. , 2005, Current opinion in cell biology.

[46]  G. Gilmartin Eukaryotic mRNA 3' processing: a common means to different ends. , 2005, Genes & development.

[47]  Michael Hampsey,et al.  A role for the CPF 3'-end processing machinery in RNAP II-dependent gene looping. , 2005, Genes & development.

[48]  Y. Hiraoka,et al.  Selective elimination of messenger RNA prevents an incidence of untimely meiosis , 2006, Nature.

[49]  Arlen W. Johnson,et al.  The role of Rat1 in coupling mRNA 3'-end processing to transcription termination: implications for a unified allosteric-torpedo model. , 2006, Genes & development.

[50]  C. Norbury,et al.  Requirement of Fission Yeast Cid14 in Polyadenylation of rRNAs , 2006, Molecular and Cellular Biology.

[51]  David Tollervey,et al.  RNA-quality control by the exosome , 2006, Nature Reviews Molecular Cell Biology.

[52]  A. Barta,et al.  Rct1, a Nuclear RNA Recognition Motif-Containing Cyclophilin, Regulates Phosphorylation of the RNA Polymerase II C-Terminal Domain , 2007, Molecular and Cellular Biology.

[53]  J. Bähler,et al.  Global Role for Polyadenylation-Assisted Nuclear RNA Degradation in Posttranscriptional Gene Silencing , 2007, Molecular and Cellular Biology.

[54]  Ronald W. Davis,et al.  High-density yeast-tiling array reveals previously undiscovered introns and extensive regulation of meiotic splicing , 2007, Proceedings of the National Academy of Sciences.

[55]  J. Mata,et al.  Transcriptional regulatory network for sexual differentiation in fission yeast , 2007, Genome Biology.

[56]  Lucie N. Hutchins,et al.  Systematic variation in mRNA 3′-processing signals during mouse spermatogenesis , 2006, Nucleic acids research.

[57]  B. Séraphin,et al.  A single subunit, Dis3, is essentially responsible for yeast exosome core activity , 2007, Nature Structural &Molecular Biology.

[58]  Steven P. Gygi,et al.  RNAi-Dependent and -Independent RNA Turnover Mechanisms Contribute to Heterochromatic Gene Silencing , 2007, Cell.

[59]  Masayuki Yamamoto,et al.  Molecular mechanisms underlying the mitosis–meiosis decision , 2007, Chromosome Research.

[60]  I. Goodhead,et al.  Dynamic repertoire of a eukaryotic transcriptome surveyed at single-nucleotide resolution , 2008, Nature.

[61]  Promoter-driven splicing regulation in fission yeast , 2008 .