title: A Pre-mRNA degradation pathway that selectively targets intron-containing genes requires the nuclear poly(A)-binding protein.
abstract: General discard pathways eliminate unprocessed and irregular pre-mRNAs to control the quality of gene expression. In contrast to such general pre-mRNA decay, we describe here a nuclear pre-mRNA degradation pathway that controls the expression of select intron-containing genes. We show that the fission yeast nuclear poly(A)-binding protein, Pab2, and the nuclear exosome subunit, Rrp6, are the main factors involved in this polyadenylation-dependent pre-mRNA degradation pathway. Transcriptome analysis and intron swapping experiments revealed that inefficient splicing is important to dictate susceptibility to Pab2-dependent pre-mRNA decay. We also show that negative splicing regulation can promote the poor splicing efficiency required for this pre-mRNA decay pathway, and in doing so, we identified a mechanism of cross-regulation between paralogous ribosomal proteins through nuclear pre-mRNA decay. Our findings unveil a layer of regulation in the nucleus in which the turnover of specific pre-mRNAs, besides the turnover of mature mRNAs, is used to control gene expression.
authors: RNA Group, Department of Biochemistry, Université de Sherbrooke, Sherbrooke, Québec J1H 5N4, Canada.
authors: Caroline
authors: C
authors: Lemieux
authors: Samuel
authors: S
authors: Marguerat
authors: Jennifer
authors: J
authors: Lafontaine
authors: Nicolas
authors: N
authors: Barbezier
authors: Jürg
authors: J
authors: Bähler
authors: Francois
authors: F
authors: Bachand
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D005095:Exoribonucleases / Q000235:genetics*; D063326:Exosome Multienzyme Ribonuclease Complex; D005786:Gene Expression Regulation; D015966:Gene Expression Regulation, Fungal; D007438:Introns; D008957:Models, Genetic; D011061:Poly A / Q000737:chemistry*; D039103:Poly(A)-Binding Protein II / Q000235:genetics*; D039102:Poly(A)-Binding Proteins / Q000378:metabolism*; D026723:Polyadenylation; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing; D012270:Ribosomes / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors
chemical_list: D039103:Poly(A)-Binding Protein II; D039102:Poly(A)-Binding Proteins; D012322:RNA Precursors; D029701:Saccharomyces cerevisiae Proteins; D011061:Poly A; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C112610:RRP6 protein, S cerevisiae