RRC ID |
35471
|
著者 |
Chalamcharla VR, Folco HD, Dhakshnamoorthy J, Grewal SI.
|
タイトル |
Conserved factor Dhp1/Rat1/Xrn2 triggers premature transcription termination and nucleates heterochromatin to promote gene silencing.
|
ジャーナル |
Proc Natl Acad Sci U S A
|
Abstract |
Cotranscriptional RNA processing and surveillance factors mediate heterochromatin formation in diverse eukaryotes. In fission yeast, RNAi machinery and RNA elimination factors including the Mtl1-Red1 core and the exosome are involved in facultative heterochromatin assembly; however, the exact mechanisms remain unclear. Here we show that RNA elimination factors cooperate with the conserved exoribonuclease Dhp1/Rat1/Xrn2, which couples pre-mRNA 3'-end processing to transcription termination, to promote premature termination and facultative heterochromatin formation at meiotic genes. We also find that Dhp1 is critical for RNAi-mediated heterochromatin assembly at retroelements and regulated gene loci and facilitates the formation of constitutive heterochromatin at centromeric and mating-type loci. Remarkably, our results reveal that Dhp1 interacts with the Clr4/Suv39h methyltransferase complex and acts directly to nucleate heterochromatin. Our work uncovers a previously unidentified role for 3'-end processing and transcription termination machinery in gene silencing through premature termination and suggests that noncanonical transcription termination by Dhp1 and RNA elimination factors is linked to heterochromatin assembly. These findings have important implications for understanding silencing mechanisms targeting genes and repeat elements in higher eukaryotes.
|
巻・号 |
112(51)
|
ページ |
15548-55
|
公開日 |
2015-12-22
|
DOI |
10.1073/pnas.1522127112
|
PII |
1522127112
|
PMID |
26631744
|
PMC |
PMC4697380
|
MeSH |
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism
Chromatin Assembly and Disassembly / genetics
Chromatin Assembly and Disassembly / physiology
Exoribonucleases / genetics
Exoribonucleases / metabolism*
Gene Silencing*
Genes, Fungal
Heterochromatin / genetics
Heterochromatin / metabolism
Histone-Lysine N-Methyltransferase
Introns
Meiosis / genetics
Methyltransferases / genetics
Methyltransferases / metabolism
Mutation
RNA 3' End Processing
RNA, Fungal / genetics
RNA, Fungal / metabolism
Retroelements
Schizosaccharomyces / genetics*
Schizosaccharomyces / growth & development
Schizosaccharomyces / metabolism*
Schizosaccharomyces pombe Proteins / genetics
Schizosaccharomyces pombe Proteins / metabolism*
Transcription Termination, Genetic*
|
IF |
9.412
|
引用数 |
29
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
酵母 |
FY13308 |