5o8m
Crystal structure of the MmI1 YTH domain
Structural highlights
FunctionMMI1_SCHPO RNA-binding protein that recognizes and binds N6-methyladenosine (m6A)-containing RNAs, a modification present at internal sites of mRNAs and some non-coding RNAs (By similarity). Required for elemination of certain meiosis-specific mRNAs in an early event following transcription. May bind to the cis-acting region (DSR) of the mRNA, activating the nuclear exosome which may lead to the degradation of the transcript from the 3' region (PubMed:16823445).[UniProtKB:Q06390][1] Publication Abstract from PubMedLong non-coding RNAs (lncRNAs) regulating gene expression at the chromatin level are widespread among eukaryotes. However, their functions and the mechanisms by which they act are not fully understood. Here, we identify new fission yeast regulatory lncRNAs that are targeted, at their site of transcription, by the YTH domain of the RNA-binding protein Mmi1 and degraded by the nuclear exosome. We uncover that one of them, nam1, regulates entry into sexual differentiation. Importantly, we demonstrate that Mmi1 binding to this lncRNA not only triggers its degradation but also mediates its transcription termination, thus preventing lncRNA transcription from invading and repressing the downstream gene encoding a mitogen-activated protein kinase kinase kinase (MAPKKK) essential to sexual differentiation. In addition, we show that Mmi1-mediated termination of lncRNA transcription also takes place at pericentromeric regions where it contributes to heterochromatin gene silencing together with RNA interference (RNAi). These findings reveal an important role for selective termination of lncRNA transcription in both euchromatic and heterochromatic lncRNA-based gene silencing processes. Selective termination of lncRNA transcription promotes heterochromatin silencing and cell differentiation.,Touat-Todeschini L, Shichino Y, Dangin M, Thierry-Mieg N, Gilquin B, Hiriart E, Sachidanandam R, Lambert E, Brettschneider J, Reuter M, Kadlec J, Pillai R, Yamashita A, Yamamoto M, Verdel A EMBO J. 2017 Sep 1;36(17):2626-2641. doi: 10.15252/embj.201796571. Epub 2017 Aug , 1. PMID:28765164[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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