期刊
MOLECULAR CELL
卷 74, 期 3, 页码 521-+出版社
CELL PRESS
DOI: 10.1016/j.molcel.2019.03.001
关键词
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资金
- NIH [R01 GM081025]
- University of Michigan Comprehensive Cancer Center/Biointerfaces Institute research grant
- NIH cellular and molecular biology training grant [T32-GM007315]
- Prostate Cancer Foundation
- Howard Hughes Medical Institute
- AACR-Bayer prostate cancer research fellowship [16-40-44-PITC]
- Department of Defense postdoctoral fellowship [W81XWH-16-1-0195]
- NSF MRI-ID grant [DBI-0959823]
Cellular RNAs often colocalize with cytoplasmic, membrane-less ribonucleoprotein (RNP) granules enriched for RNA-processing enzymes, termed processing bodies (PBs). Here we track the dynamic localization of individual miRNAs, mRNAs, and long non-coding RNAs (lncRNAs) to PBs using intracellular single-molecule fluorescence microscopy. We find that unused miRNAs stably bind to PBs, whereas functional miRNAs, repressed mRNAs, and lncRNAs both transiently and stably localize within either the core or periphery of PBs, albeit to different extents. Consequently, translation potential and 3' versus 5' placement of miRNA target sites significantly affect the PB localization dynamics of mRNAs. Using computational modeling and supporting experimental approaches, we show that partitioning in the PB phase attenuates mRNA silencing, suggesting that physiological mRNA turnover occurs predominantly outside of PBs. Instead, our data support a PB role in sequestering unused miRNAs for surveillance and provide a framework for investigating the dynamic assembly of RNP granules by phase separation at single-molecule resolution.
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