期刊
NATURE COMMUNICATIONS
卷 13, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-022-32542-3
关键词
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资金
- CNRS ATIP-Avenir program
- ANR MTREC [ANR-21-CE11-0021]
- ANR RNAGermSilence [ANR-13-BSV2-0012]
- Labex GRAL [ANR-10-LABX-49-01]
- People Program (Marie Curie Actions) of the European Union's Seventh Framework Program under REA grant agreement [PCOFUND-GA-2013-609102]
- Center National de la Recherche Scientifique (IR-RMN-THC Fr3050)
- FRISBI [ANR-10-INBS-0005-02]
- GRAL within the University Grenoble Alpes graduate school (Ecoles Universitaires de Recherche) CBH-EUR-GS [ANR-17-EURE-0003]
- Agence Nationale de la Recherche (ANR) [ANR-21-CE11-0021, ANR-13-BSV2-0012] Funding Source: Agence Nationale de la Recherche (ANR)
In this study, the authors characterized the structural and functional features of three interfaces of the Red1 protein in the MTREC/PAXT nuclear complex, providing mechanistic insights into the conserved features of MTREC/PAXT architecture. These findings contribute to a better understanding of the mechanisms of RNA degradation.
Unwanted RNA transcripts are targeted for degradation by nuclear complexes such as MTREC/PAXT. Here, the authors structurally and functionally characterized three interfaces of the scaffold protein Red1, providing mechanistic insights into conserved features of MTREC/PAXT architecture. To eliminate specific or aberrant transcripts, eukaryotes use nuclear RNA-targeting complexes that deliver them to the exosome for degradation. S. pombe MTREC, and its human counterpart PAXT, are key players in this mechanism but inner workings of these complexes are not understood in sufficient detail. Here, we present an NMR structure of an MTREC scaffold protein Red1 helix-turn-helix domain bound to the Iss10 N-terminus and show this interaction is required for proper cellular growth and meiotic mRNA degradation. We also report a crystal structure of a Red1-Ars2 complex explaining mutually exclusive interactions of hARS2 with various ED/EGEI/L motif-possessing RNA regulators, including hZFC3H1 of PAXT, hFLASH or hNCBP3. Finally, we show that both Red1 and hZFC3H1 homo-dimerize via their coiled-coil regions indicating that MTREC and PAXT likely function as dimers. Our results, combining structures of three Red1 interfaces with in vivo studies, provide mechanistic insights into conserved features of MTREC/PAXT architecture.
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