期刊
NUCLEIC ACIDS RESEARCH
卷 50, 期 12, 页码 7013-7033出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkac538
关键词
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资金
- Intramural Research Program of the National Institute on Aging, National Institutes of Health [Z01 AG000657-08]
- Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health [ZO1 DK015602-09]
- NIH [Z01 AG000657-08]
This study investigates the post-transcriptional influence of topoisomerase 3 beta (TOP3B) and associated proteins on mRNA translation and turnover. The findings suggest that TOP3B and TDRD3 have a stronger coordination in mRNA regulation compared to FMRP. The study also reveals that TOP3B can stabilize a subset of target mRNAs and has a complex effect on mRNA translation, which is partly linked to its ability to change the topology of mRNAs.
Topoisomerase 3 beta (TOP3B) and TDRD3 form a dual-activity topoisomerase complex that interacts with FMRP and can change the topology of both DNA and RNA. Here, we investigated the post-transcriptional influence of TOP3B and associated proteins on mRNA translation and turnover. First, we discovered that in human HCT116 colon cancer cells, knock-out (KO) of TOP3B had similar effects on mRNA turnover and translation as did TDRD3-KO, while FMRP-KO resulted in rather distinct effects, indicating that TOP3B had stronger coordination with TDRD3 than FMRP in mRNA regulation. Second, we identified TOP3B-bound mRNAs in HCT116 cells; we found that while TOP3B did not directly influence the stability or translation of most TOP3B target mRNAs, it stabilized a subset of target mRNAs but had a more complex effect on translation-enhancing for some mRNAs whereas reducing for others. Interestingly, a point mutation that specifically disrupted TOP3B catalytic activity only partially recapitulated the effects of TOP3B-KO on mRNA stability and translation, suggesting that the impact of TOP3B on target mRNAs is partly linked to its ability to change topology of mRNAs. Collectively, our data suggest that TOP3B-TDRD3 can regulate mRNA translation and turnover by mechanisms that are dependent and independent of topoisomerase activity.
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