The Dynamics of Cytoplasmic mRNA Metabolism
© 2019 Elsevier Inc. For all but a few mRNAs, the dynamics of metabolism are unknown. Here, we developed an experimental and analytical framework for examining these dynamics for mRNAs from thousands of genes. mRNAs of mouse fibroblasts exit the nucleus with diverse intragenic and intergenic poly(A)...
| Main Authors: | , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
| Published: |
Elsevier BV
2021
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| Online Access: | https://hdl.handle.net/1721.1/136648 |
| _version_ | 1811094753127694336 |
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| author | Eisen, Timothy J Eichhorn, Stephen W Subtelny, Alexander O Lin, Kathy S McGeary, Sean E Gupta, Sumeet Bartel, David P |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Eisen, Timothy J Eichhorn, Stephen W Subtelny, Alexander O Lin, Kathy S McGeary, Sean E Gupta, Sumeet Bartel, David P |
| author_sort | Eisen, Timothy J |
| collection | MIT |
| description | © 2019 Elsevier Inc. For all but a few mRNAs, the dynamics of metabolism are unknown. Here, we developed an experimental and analytical framework for examining these dynamics for mRNAs from thousands of genes. mRNAs of mouse fibroblasts exit the nucleus with diverse intragenic and intergenic poly(A)-tail lengths. Once in the cytoplasm, they have a broad (1000-fold) range of deadenylation rate constants, which correspond to cytoplasmic lifetimes. Indeed, with few exceptions, degradation appears to occur primarily through deadenylation-linked mechanisms, with little contribution from either endonucleolytic cleavage or deadenylation-independent decapping. Most mRNA molecules degrade only after their tail lengths fall below 25 nt. Decay rate constants of short-tailed mRNAs vary broadly (1000-fold) and are larger for short-tailed mRNAs that have previously undergone more rapid deadenylation. This coupling helps clear rapidly deadenylated mRNAs, enabling the large range in deadenylation rate constants to impart a similarly large range in stabilities. mRNA decay helps determine the extent of mRNA accumulation and ultimately the amount of protein produced. The dynamics of mRNA decay—involving tail-length shortening and then decay of the mRNA body—are largely unknown. Eisen et al. use high-throughput methods to uncover these dynamics for thousands of endogenous mRNAs. |
| first_indexed | 2024-09-23T16:04:32Z |
| format | Article |
| id | mit-1721.1/136648 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T16:04:32Z |
| publishDate | 2021 |
| publisher | Elsevier BV |
| record_format | dspace |
| spelling | mit-1721.1/1366482023-12-19T21:19:09Z The Dynamics of Cytoplasmic mRNA Metabolism Eisen, Timothy J Eichhorn, Stephen W Subtelny, Alexander O Lin, Kathy S McGeary, Sean E Gupta, Sumeet Bartel, David P Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Massachusetts Institute of Technology. Computational and Systems Biology Program © 2019 Elsevier Inc. For all but a few mRNAs, the dynamics of metabolism are unknown. Here, we developed an experimental and analytical framework for examining these dynamics for mRNAs from thousands of genes. mRNAs of mouse fibroblasts exit the nucleus with diverse intragenic and intergenic poly(A)-tail lengths. Once in the cytoplasm, they have a broad (1000-fold) range of deadenylation rate constants, which correspond to cytoplasmic lifetimes. Indeed, with few exceptions, degradation appears to occur primarily through deadenylation-linked mechanisms, with little contribution from either endonucleolytic cleavage or deadenylation-independent decapping. Most mRNA molecules degrade only after their tail lengths fall below 25 nt. Decay rate constants of short-tailed mRNAs vary broadly (1000-fold) and are larger for short-tailed mRNAs that have previously undergone more rapid deadenylation. This coupling helps clear rapidly deadenylated mRNAs, enabling the large range in deadenylation rate constants to impart a similarly large range in stabilities. mRNA decay helps determine the extent of mRNA accumulation and ultimately the amount of protein produced. The dynamics of mRNA decay—involving tail-length shortening and then decay of the mRNA body—are largely unknown. Eisen et al. use high-throughput methods to uncover these dynamics for thousands of endogenous mRNAs. 2021-10-27T20:36:26Z 2021-10-27T20:36:26Z 2020 2021-07-14T14:15:09Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/136648 en 10.1016/J.MOLCEL.2019.12.005 Molecular Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV Elsevier |
| spellingShingle | Eisen, Timothy J Eichhorn, Stephen W Subtelny, Alexander O Lin, Kathy S McGeary, Sean E Gupta, Sumeet Bartel, David P The Dynamics of Cytoplasmic mRNA Metabolism |
| title | The Dynamics of Cytoplasmic mRNA Metabolism |
| title_full | The Dynamics of Cytoplasmic mRNA Metabolism |
| title_fullStr | The Dynamics of Cytoplasmic mRNA Metabolism |
| title_full_unstemmed | The Dynamics of Cytoplasmic mRNA Metabolism |
| title_short | The Dynamics of Cytoplasmic mRNA Metabolism |
| title_sort | dynamics of cytoplasmic mrna metabolism |
| url | https://hdl.handle.net/1721.1/136648 |
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