CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene Silencing.

Szczegóły
Abstrakt

Tytuł:: CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene Silencing.
Autorzy:: Vo TV; Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Dhakshnamoorthy J; Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Larkin M; Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Zofall M; Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Thillainadesan G; Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Balachandran V; Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Holla S; Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Wheeler D; Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Grewal SIS; Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA. Electronic address: .
Źródło:: Cell reports [Cell Rep] 2019 Jul 02; Vol. 28 (1), pp. 267-281.e5.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural
Język:: English
Imprint Name(s):: Original Publication: [Cambridge, MA] : Cell Press, c 2012-
MeSH Terms:: Gene Silencing*
Transcription Termination, Genetic*
Heterochromatin/*metabolism
RNA Polymerase II/*metabolism
Schizosaccharomyces/*genetics
Schizosaccharomyces pombe Proteins/*metabolism
mRNA Cleavage and Polyadenylation Factors/*metabolism
Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Chromatin Assembly and Disassembly/genetics ; Exoribonucleases/genetics ; Exoribonucleases/metabolism ; Gene Expression Regulation, Fungal ; Histone-Lysine N-Methyltransferase/genetics ; Histone-Lysine N-Methyltransferase/metabolism ; Meiosis/genetics ; Phosphoprotein Phosphatases/genetics ; Phosphoprotein Phosphatases/metabolism ; RNA Interference ; RNA, Long Noncoding/genetics ; RNA, Long Noncoding/metabolism ; Schizosaccharomyces/metabolism ; Schizosaccharomyces pombe Proteins/genetics ; mRNA Cleavage and Polyadenylation Factors/genetics
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Grant Information:: Z01 BC010523 United States ImNIH Intramural NIH HHS; ZIA BC011208 United States ImNIH Intramural NIH HHS; ZIA BC010523 United States ImNIH Intramural NIH HHS; Z99 CA999999 United States ImNIH Intramural NIH HHS; FI2 GM123947 United States GM NIGMS NIH HHS
Contributed Indexing:: Keywords: CPF; Mmi1; RNA polymerase II; YTH; facultative; gene silencing; heterochromatin; histone methylation; pre-mRNA processing; transcription termination
Substance Nomenclature:: 0 (Cell Cycle Proteins)
0 (Heterochromatin)
0 (Mmi1 protein, S pombe)
0 (RNA, Long Noncoding)
0 (Schizosaccharomyces pombe Proteins)
0 (mRNA Cleavage and Polyadenylation Factors)
EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
EC 2.1.1.43 (clr4 protein, S pombe)
EC 2.7.7.- (RNA Polymerase II)
EC 3.1.- (Exoribonucleases)
EC 3.1.- (dhp1protein, S pombe)
EC 3.1.3.16 (Phosphoprotein Phosphatases)
EC 3.1.3.16 (ssu72 protein, S pombe)
Entry Date(s):: Date Created: 20190704 Date Completed: 20200827 Latest Revision: 20210110
Update Code:: 20240105
PubMed Central ID:: PMC7457318
DOI:: 10.1016/j.celrep.2019.05.107
PMID:: 31269446
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In eukaryotic genomes, heterochromatin is targeted by RNAi machinery and/or by pathways requiring RNA elimination and transcription termination factors. However, a direct connection between termination machinery and RNA polymerase II (RNAPII) transcriptional activity at heterochromatic loci has remained elusive. Here, we show that, in fission yeast, the conserved cleavage and polyadenylation factor (CPF) is a key component involved in RNAi-independent assembly of constitutive and facultative heterochromatin domains and that CPF is broadly required to silence genes regulated by Clr4 SUV39H . Remarkably, CPF is recruited to non-canonical termination sites within the body of genes by the YTH family RNA-binding protein Mmi1 and is required for RNAPII transcription termination and facultative heterochromatin assembly. CPF loading by Mmi1 also promotes the selective termination of long non-coding RNAs that regulate gene expression in cis. These analyses delineate a mechanism in which CPF loaded onto non-canonical termination sites specifies targets of heterochromatin assembly and gene silencing.
(Published by Elsevier Inc.)

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