Widespread Influence of 3′-End Structures on Mammalian mRNA Processing and Stability
Name
nihms875423.pdf
Size
1.42 MB
Format
Adobe PDF
Checksum (MD5)
ea298533b8da8ac2b4dd3c2446580f43
Author(s)
Wu, Xuebing
Bartel, David P.
Bartel, David
Date Issued
May 2017
Journal
Cell
Publisher
Elsevier BV
Citation
Wu, Xuebing, and David P. Bartel. “Widespread Influence of 3′-End Structures on Mammalian mRNA Processing and Stability.” Cell 169, 5 (May 2017): 905–917 © 2017 Elsevier Inc
Version
Author's final manuscript
Abstract
The physiological relevance of structures within mammalian mRNAs has been elusive, as these mRNAs are less folded in cells than in vitro and have predicted secondary structures no more stable than those of random sequences. Here, we investigate the possibility that mRNA structures facilitate the 3′-end processing of thousands of human mRNAs by juxtaposing poly(A) signals (PASs) and cleavage sites that are otherwise too far apart. We find that RNA structures are predicted to be more prevalent within these extended 3′-end regions than within PAS-upstream regions and indeed are substantially more folded within cells, as determined by intracellular probing. Analyses of thousands of ectopically expressed variants demonstrate that this folding both enhances processing and increases mRNA metabolic stability. Even folds with predicted stabilities resembling those of random sequences can enhance processing. Structure-controlled processing can also regulate neighboring gene expression. Thus, RNA structure has widespread roles in mammalian mRNA biogenesis and metabolism. Keywords: mRNA structure; in vivo structural probing; DMS-seq; mRNA 3′ end processing; cleavage and polyadenylation; mRNA stability; RNA metabolic labeling; CRISPR/Cas9;
high-throughput analysis
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.CELL.2017.04.036
