RNAi-dependent and -independent RNA turnover mechanisms contribute to heterochromatic gene silencing. 2007

Marc Bühler, and Wilhelm Haas, and Steven P Gygi, and Danesh Moazed
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.

In fission yeast, the RNAi pathway is required for heterochromatin-dependent silencing of transgene insertions at centromeric repeats and acts together with other pathways to silence transgenes at the silent mating-type locus. Here, we show that transgene transcripts at centromeric repeats are processed into siRNAs and are therefore direct targets of RNAi. Furthermore, we show that Cid14, a member of the Trf4/5 family of poly(A) polymerases, has poly(A) polymerase activity that is required for heterochromatic gene silencing. Surprisingly, while siRNA levels in cid14Delta cells are dramatically reduced, the structural integrity of heterochromatin appears to be preserved. Cid14 resides in a complex similar to the TRAMP complex found in budding yeast, which is part of a nuclear surveillance mechanism that degrades aberrant transcripts. Our findings indicate that polyadenylation by a TRAMP-like complex contributes to robust silencing of heterochromatic genes in fission yeast via the recruitment of the exosome and/or the RNAi machinery.

UI MeSH Term Description Entries
D011062 Polynucleotide Adenylyltransferase An enzyme that catalyzes the synthesis of polyadenylic acid from ATP. May be due to the action of RNA polymerase (EC 2.7.7.6) or polynucleotide adenylyltransferase (EC 2.7.7.19). EC 2.7.7.19. Poly A Polymerase,Polyadenylate Polymerase,Polyadenylate Synthetase,ATP-RNA Adenylyltransferase,ATP RNA Adenylyltransferase,Adenylyltransferase, ATP-RNA,Adenylyltransferase, Polynucleotide,Polymerase, Poly A,Polymerase, Polyadenylate,Synthetase, Polyadenylate
D006570 Heterochromatin The portion of chromosome material that remains condensed and is transcriptionally inactive during INTERPHASE. Heterochromatins
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated
D012568 Schizosaccharomyces A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales. Fission Yeast,Schizosaccharomyces malidevorans,Schizosaccharomyces pombe,Yeast, Fission,S pombe,Fission Yeasts
D015536 Down-Regulation A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins. Receptor Down-Regulation,Down-Regulation (Physiology),Downregulation,Down Regulation,Down-Regulation, Receptor
D015966 Gene Expression Regulation, Fungal Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in fungi. Fungal Gene Expression Regulation,Regulation of Gene Expression, Fungal,Regulation, Gene Expression, Fungal
D046911 Macromolecular Substances Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure. Macromolecular Complexes,Macromolecular Compounds,Macromolecular Compounds and Complexes,Complexes, Macromolecular,Compounds, Macromolecular,Substances, Macromolecular
D020868 Gene Silencing Interruption or suppression of the expression of a gene at transcriptional or translational levels. Gene Inactivation,Inactivation, Gene,Silencing, Gene
D029702 Schizosaccharomyces pombe Proteins Proteins obtained from the species Schizosaccharomyces pombe. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes. Fission Yeast Proteins,S pombe Proteins
D034622 RNA Interference A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process. Gene Silencing, Post-Transcriptional,Post-Transcriptional Gene Silencing,Co-Suppression,Cosuppression,Posttranscriptional Gene Silencing,RNA Silencing,RNAi,Co Suppression,Gene Silencing, Post Transcriptional,Gene Silencing, Posttranscriptional,Gene Silencings, Posttranscriptional,Interference, RNA,Post Transcriptional Gene Silencing,Post-Transcriptional Gene Silencings,Silencing, Post-Transcriptional Gene

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