期刊
EMBO JOURNAL
卷 32, 期 13, 页码 1855-1868出版社
WILEY
DOI: 10.1038/emboj.2013.135
关键词
hDIS3L2; P-bodies; ribonuclease; RNA decay; Xrn1
资金
- European Union-the European Regional Development Fund
- Danish National Research Foundation
- Danish Cancer Society
- Lundbeck-Foundation
- Novo Nordisk Foundation
- Danish Council for Independent Research
- Lundbeck Foundation
- NCN Maestro grant [UMO-2011/02/A/NZ1/00001]
- Iuventus Plus research grant [IP2010 043470]
- Polish Ministry of Science and Higher Education
- Boehringer-Ingelheim
- Foundation for Polish Science
- Novo Nordisk Fonden [NNF12OC0001211] Funding Source: researchfish
Turnover of mRNA in the cytoplasm of human cells is thought to be redundantly conducted by the monomeric 5'-3' exoribonuclease hXRN1 and the 5'-3' exoribonucleolytic RNA exosome complex. However, in addition to the exosome-associated 5'-3' exonucleases hDIS3 and hDIS3L, the human genome encodes another RNase II/R domain protein-hDIS3L2. Here, we show that hDIS3L2 is an exosome-independent cytoplasmic mRNA 5'-3' exonuclease, which exhibits processive activity on structured RNA substrates in vitro. hDIS3L2 associates with hXRN1 in an RNA-dependent manner and can, like hXRN1, be found on polysomes. The impact of hDIS3L2 on cytoplasmic RNA metabolism is revealed by an increase in levels of cytoplasmic RNA processing bodies (P-bodies) upon hDIS3L2 depletion, which also increases half-lives of investigated mRNAs. Consistently, RNA sequencing (RNA-seq) analyses demonstrate that depletion of hDIS3L2, like downregulation of hXRN1 and hDIS3L, causes changed levels of multiple mRNAs. We suggest that hDIS3L2 is a key exosome-independent effector of cytoplasmic mRNA metabolism.
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