期刊
NUCLEIC ACIDS RESEARCH
卷 42, 期 6, 页码 3803-3820出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkt1308
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资金
- National Institutes of Health, National Cancer Institute [CA044059]
- Maltz Family Foundation
- Mal and Lea Bank Chair fund
- National Institutes of Health [GM060518]
- International postdoctoral fellowship from the Fondation pour la Recherche Medicale (FRM)
- NIH Training Grant [T32-GM007315]
- NIH, National Cancer Institute [CA044059]
Retrotransposons are mobile genetic elements, and their mobility can lead to genomic instability. Retrotransposon insertions are associated with a diverse range of sporadic diseases, including cancer. Thus, it is not a surprise that multiple host defense mechanisms suppress retrotransposition. The 2',5'-oligoadenylate (2-5A) synthetase (OAS)-RNase L system is a mechanism for restricting viral infections during the interferon antiviral response. Here, we investigated a potential role for the OAS-RNase L system in the restriction of retrotransposons. Expression of wild type (WT) and a constitutively active form of RNase L (N delta 385), but not a catalytically inactive RNase L mutant (R667A), impaired the mobility of engineered human LINE-1 (L1) and mouse intracisternal A-type particle retrotransposons in cultured human cells. Furthermore, WT RNase L, but not an inactive RNase L mutant (R667A), reduced L1 RNA levels and subsequent expression of the L1-encoded proteins (ORF1p and ORF2p). Consistently, confocal immunofluorescent microscopy demonstrated that WT RNase L, but not RNase L R667A, prevented formation of L1 cytoplasmic foci. Finally, siRNA-mediated depletion of endogenous RNase L in a human ovarian cancer cell line (Hey1b) increased the levels of L1 retrotransposition by similar to 2-fold. Together, these data suggest that RNase L might function as a suppressor of structurally distinct retrotransposons.
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