Widespread Influence of 3′-End Structures on Mammalian mRNA Processing and Stability
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′-...
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| Format: | Article |
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Elsevier BV
2018
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| Online Access: | http://hdl.handle.net/1721.1/116297 https://orcid.org/0000-0003-0369-5269 https://orcid.org/0000-0002-3872-2856 |
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| author | Wu, Xuebing Bartel, David P. Bartel, David |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Wu, Xuebing Bartel, David P. Bartel, David |
| author_sort | Wu, Xuebing |
| collection | MIT |
| description | 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 |
| first_indexed | 2024-09-23T15:03:18Z |
| format | Article |
| id | mit-1721.1/116297 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T15:03:18Z |
| publishDate | 2018 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1162972022-09-29T12:21:14Z Widespread Influence of 3′-End Structures on Mammalian mRNA Processing and Stability Wu, Xuebing Bartel, David P. Bartel, David Massachusetts Institute of Technology. Department of Biology Wu, Xuebing Bartel, David 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 2018-06-13T20:27:43Z 2018-06-13T20:27:43Z 2017-05 2017-03 2018-06-12T18:24:57Z Article http://purl.org/eprint/type/JournalArticle 0092-8674 1097-4172 http://hdl.handle.net/1721.1/116297 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 https://orcid.org/0000-0003-0369-5269 https://orcid.org/0000-0002-3872-2856 http://dx.doi.org/10.1016/J.CELL.2017.04.036 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC |
| spellingShingle | Wu, Xuebing Bartel, David P. Bartel, David Widespread Influence of 3′-End Structures on Mammalian mRNA Processing and Stability |
| title | Widespread Influence of 3′-End Structures on Mammalian mRNA Processing and Stability |
| title_full | Widespread Influence of 3′-End Structures on Mammalian mRNA Processing and Stability |
| title_fullStr | Widespread Influence of 3′-End Structures on Mammalian mRNA Processing and Stability |
| title_full_unstemmed | Widespread Influence of 3′-End Structures on Mammalian mRNA Processing and Stability |
| title_short | Widespread Influence of 3′-End Structures on Mammalian mRNA Processing and Stability |
| title_sort | widespread influence of 3 end structures on mammalian mrna processing and stability |
| url | http://hdl.handle.net/1721.1/116297 https://orcid.org/0000-0003-0369-5269 https://orcid.org/0000-0002-3872-2856 |
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