Negative regulation of meiotic gene expression by the nuclear poly(a)-binding protein in fission yeast.
Meiosis is a cellular differentiation process in which hundreds of genes are temporally induced. Because the expression of meiotic genes during mitosis is detrimental to proliferation, meiotic genes must be negatively regulated in the mitotic cell cycle. Yet, little is known about mechanisms used by mitotic cells to repress meiosis-specific genes. Here we show that the poly(A)-binding protein Pab2, the fission yeast homolog of mammalian PABPN1, controls the expression of several meiotic transcripts during mitotic division. Our results from chromatin immunoprecipitation and promoter-swapping experiments indicate that Pab2 controls meiotic genes post-transcriptionally. Consistently, we show that the nuclear exosome complex cooperates with Pab2 in the negative regulation of meiotic genes. We also found that Pab2 plays a role in the RNA decay pathway orchestrated by Mmi1, a previously described factor that functions in the post-transcriptional elimination of meiotic transcripts. Our results support a model in which Mmi1 selectively targets meiotic transcripts for degradation via Pab2 and the exosome. Our findings have therefore uncovered a mode of gene regulation whereby a poly(A)-binding protein promotes RNA degradation in the nucleus to prevent untimely expression.
St-André
Olivier
O
RNA Group, Université de Sherbrooke, Department of Biochemistry, Sherbrooke, Québec J1H 5N4, Canada.
Lemieux
Caroline
C
Perreault
Audrey
A
Lackner
Daniel H
DH
Bähler
Jürg
J
Bachand
François
F
D002467:Cell Nucleus / Q000378:metabolism*; D055354:Exosomes / Q000378:metabolism; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D008540:Meiosis / Q000235:genetics*; D039103:Poly(A)-Binding Protein II / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D022661:RNA, Untranslated / Q000235:genetics; D016601:RNA-Binding Proteins / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology* / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism
C512176:Mmi1 protein, S pombe; D039103:Poly(A)-Binding Protein II; D012333:RNA, Messenger; D022661:RNA, Untranslated; D016601:RNA-Binding Proteins; D029702:Schizosaccharomyces pombe Proteins; D039221:mRNA Cleavage and Polyadenylation Factors; C088896:mei2 protein, S pombe