The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes
Background: All mRNAs are bound in vivo by proteins to form mRNA-protein complexes (mRNPs), but changes in the composition of mRNPs during posttranscriptional regulation remain largely unexplored. Here, we have analyzed, on a transcriptome-wide scale, how microRNA-mediated repression modulates the a...
| Main Authors: | , , , , , , , , , |
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Biomed Central Ltd.
2018
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| Online Access: | http://hdl.handle.net/1721.1/116461 https://orcid.org/0000-0001-5029-5909 https://orcid.org/0000-0002-3872-2856 |
| _version_ | 1811086057213526016 |
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| author | Wang, Miranda Lugowski, Andrew Nicholson, Beth Laver, John D. Sidhu, Sachdev S. Smibert, Craig A. Lipshitz, Howard D. Subtelny, Alexander Orest Rissland, Olivia S. Bartel, David |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Wang, Miranda Lugowski, Andrew Nicholson, Beth Laver, John D. Sidhu, Sachdev S. Smibert, Craig A. Lipshitz, Howard D. Subtelny, Alexander Orest Rissland, Olivia S. Bartel, David |
| author_sort | Wang, Miranda |
| collection | MIT |
| description | Background: All mRNAs are bound in vivo by proteins to form mRNA-protein complexes (mRNPs), but changes in the composition of mRNPs during posttranscriptional regulation remain largely unexplored. Here, we have analyzed, on a transcriptome-wide scale, how microRNA-mediated repression modulates the associations of the core mRNP components eIF4E, eIF4G, and PABP and of the decay factor DDX6 in human cells. Results: Despite the transient nature of repressed intermediates, we detect significant changes in mRNP composition, marked by dissociation of eIF4G and PABP, and by recruitment of DDX6. Furthermore, although poly(A)-tail length has been considered critical in post-transcriptional regulation, differences in steady-state tail length explain little of the variation in either PABP association or mRNP organization more generally. Instead, relative occupancy of core components correlates best with gene expression. Conclusions: These results indicate that posttranscriptional regulatory factors, such as microRNAs, influence the associations of PABP and other core factors, and do so without substantially affecting steady-state tail length. |
| first_indexed | 2024-09-23T13:20:13Z |
| format | Article |
| id | mit-1721.1/116461 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T13:20:13Z |
| publishDate | 2018 |
| publisher | Biomed Central Ltd. |
| record_format | dspace |
| spelling | mit-1721.1/1164612022-09-28T13:31:24Z The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes Wang, Miranda Lugowski, Andrew Nicholson, Beth Laver, John D. Sidhu, Sachdev S. Smibert, Craig A. Lipshitz, Howard D. Subtelny, Alexander Orest Rissland, Olivia S. Bartel, David Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Subtelny, Alexander Orest Rissland, Olivia S. Bartel, David Background: All mRNAs are bound in vivo by proteins to form mRNA-protein complexes (mRNPs), but changes in the composition of mRNPs during posttranscriptional regulation remain largely unexplored. Here, we have analyzed, on a transcriptome-wide scale, how microRNA-mediated repression modulates the associations of the core mRNP components eIF4E, eIF4G, and PABP and of the decay factor DDX6 in human cells. Results: Despite the transient nature of repressed intermediates, we detect significant changes in mRNP composition, marked by dissociation of eIF4G and PABP, and by recruitment of DDX6. Furthermore, although poly(A)-tail length has been considered critical in post-transcriptional regulation, differences in steady-state tail length explain little of the variation in either PABP association or mRNP organization more generally. Instead, relative occupancy of core components correlates best with gene expression. Conclusions: These results indicate that posttranscriptional regulatory factors, such as microRNAs, influence the associations of PABP and other core factors, and do so without substantially affecting steady-state tail length. National Institutes of Health (U.S.) (Grant K99GM102319) National Institutes of Health (U.S.) (Grant T32GM007753) National Institutes of Health (U.S.) (Grant R01GM067031) National Institutes of Health (U.S.) (Grant R35GM118135) Natural Sciences and Engineering Research Council of Canada (Discovery Grant) 2018-06-21T13:41:48Z 2018-06-21T13:41:48Z 2017-10 2017-05 2018-06-12T18:09:47Z Article http://purl.org/eprint/type/JournalArticle 1474-760X http://hdl.handle.net/1721.1/116461 Rissland, Olivia S., et al. “The Influence of MicroRNAs and Poly(A) Tail Length on Endogenous MRNA–Protein Complexes.” Genome Biology, vol. 18, no. 1, Dec. 2017. © 2017 The Authors https://orcid.org/0000-0001-5029-5909 https://orcid.org/0000-0002-3872-2856 http://dx.doi.org/10.1186/s13059-017-1330-z Genome Biology Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Biomed Central Ltd. BioMedCentral |
| spellingShingle | Wang, Miranda Lugowski, Andrew Nicholson, Beth Laver, John D. Sidhu, Sachdev S. Smibert, Craig A. Lipshitz, Howard D. Subtelny, Alexander Orest Rissland, Olivia S. Bartel, David The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes |
| title | The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes |
| title_full | The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes |
| title_fullStr | The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes |
| title_full_unstemmed | The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes |
| title_short | The influence of microRNAs and poly(A) tail length on endogenous mRNA–protein complexes |
| title_sort | influence of micrornas and poly a tail length on endogenous mrna protein complexes |
| url | http://hdl.handle.net/1721.1/116461 https://orcid.org/0000-0001-5029-5909 https://orcid.org/0000-0002-3872-2856 |
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