title: Enhancer of Rudimentary Cooperates with Conserved RNA-Processing Factors to Promote Meiotic mRNA Decay and Facultative Heterochromatin Assembly.
abstract: Erh1, the fission yeast homolog of Enhancer of rudimentary, is implicated in meiotic mRNA elimination during vegetative growth, but its function is poorly understood. We show that Erh1 and the RNA-binding protein Mmi1 form a stoichiometric complex, called the Erh1-Mmi1 complex (EMC), to promote meiotic mRNA decay and facultative heterochromatin assembly. To perform these functions, EMC associates with two distinct complexes, Mtl1-Red1 core (MTREC) and CCR4-NOT. Whereas MTREC facilitates assembly of heterochromatin islands coating meiotic genes silenced by the nuclear exosome, CCR4-NOT promotes RNAi-dependent heterochromatin domain (HOOD) formation at EMC-target loci. CCR4-NOT also assembles HOODs at retrotransposons and regulated genes containing cryptic introns. We find that CCR4-NOT facilitates HOOD assembly through its association with the conserved Pir2/ARS2 protein, and also maintains rDNA integrity and silencing by promoting heterochromatin formation. Our results reveal connections among Erh1, CCR4-NOT, Pir2/ARS2, and RNAi, which target heterochromatin to regulate gene expression and protect genome integrity.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Gobi
authors.initials: G
authors.lastname: Thillainadesan
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Venkata R
authors.initials: VR
authors.lastname: Chalamcharla
authors.affiliation: Laboratory of Proteomics and Analytical Technologies, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Zhaojing
authors.initials: Z
authors.lastname: Meng
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Vanivilasini
authors.initials: V
authors.lastname: Balachandran
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA.
authors.forename: Jothy
authors.initials: J
authors.lastname: Dhakshnamoorthy
authors.affiliation: Laboratory of Proteomics and Analytical Technologies, Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: grewals@mail.nih.gov.
authors.forename: Shiv I S
authors.initials: SIS
authors.lastname: Grewal
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D006570:Heterochromatin / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis; D009154:Mutation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D034622:RNA Interference; D020871:RNA Stability; D012331:RNA, Fungal / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D018626:Retroelements; D012568:Schizosaccharomyces / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D004275:DNA, Ribosomal; C000609221:Erh1 protein, S pombe; D006570:Heterochromatin; C512176:Mmi1 protein, S pombe; D012331:RNA, Fungal; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C586176:Red1 protein, S pombe; D018626:Retroelements; D029702:Schizosaccharomyces pombe Proteins; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors; C088896:mei2 protein, S pombe