Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting
MicroRNA (miRNA) regulation clearly impacts animal development, but the extent to which development—with its resulting diversity of cellular contexts—impacts miRNA regulation is unclear. Here, we compared cohorts of genes repressed by the same miRNAs in different cell lines and tissues and found tha...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2015
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| Online Access: | http://hdl.handle.net/1721.1/96328 https://orcid.org/0000-0002-3872-2856 |
| _version_ | 1826210230869950464 |
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| author | Nam, Jin-Wu Rissland, Olivia S. Abreu-Goodger, Cei Jan, Calvin H. Agarwal, Vikram Yildirim, Muhammed A. Rodriguez, Antony Koppstein, David Neal Pira Bartel, David Rissland, Olivia S. Jan, Calvin H. Yildirim, Muhammed A. |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program Nam, Jin-Wu Rissland, Olivia S. Abreu-Goodger, Cei Jan, Calvin H. Agarwal, Vikram Yildirim, Muhammed A. Rodriguez, Antony Koppstein, David Neal Pira Bartel, David Rissland, Olivia S. Jan, Calvin H. Yildirim, Muhammed A. |
| author_sort | Nam, Jin-Wu |
| collection | MIT |
| description | MicroRNA (miRNA) regulation clearly impacts animal development, but the extent to which development—with its resulting diversity of cellular contexts—impacts miRNA regulation is unclear. Here, we compared cohorts of genes repressed by the same miRNAs in different cell lines and tissues and found that target repertoires were largely unaffected, with secondary effects explaining most of the differential responses detected. Outliers resulting from differential direct targeting were often attributable to alternative 3′ UTR isoform usage that modulated the presence of miRNA sites. More inclusive examination of alternative 3′ UTR isoforms revealed that they influence ~10% of predicted targets when comparing any two cell types. Indeed, considering alternative 3′ UTR isoform usage improved prediction of targeting efficacy significantly beyond the improvements observed when considering constitutive isoform usage. Thus, although miRNA targeting is remarkably consistent in different cell types, considering the 3′ UTR landscape helps predict targeting efficacy and explain differential regulation that is observed. |
| first_indexed | 2024-09-23T14:46:12Z |
| format | Article |
| id | mit-1721.1/96328 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:46:12Z |
| publishDate | 2015 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/963282022-09-29T10:25:01Z Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting Nam, Jin-Wu Rissland, Olivia S. Abreu-Goodger, Cei Jan, Calvin H. Agarwal, Vikram Yildirim, Muhammed A. Rodriguez, Antony Koppstein, David Neal Pira Bartel, David Rissland, Olivia S. Jan, Calvin H. Yildirim, Muhammed A. Massachusetts Institute of Technology. Computational and Systems Biology Program Massachusetts Institute of Technology. Department of Biology Whitehead Institute for Biomedical Research Nam, Jin-Wu Rissland, Olivia S. Koppstein, David Neal Pira Jan, Calvin H. Yildirim, Muhammed A. Bartel, David MicroRNA (miRNA) regulation clearly impacts animal development, but the extent to which development—with its resulting diversity of cellular contexts—impacts miRNA regulation is unclear. Here, we compared cohorts of genes repressed by the same miRNAs in different cell lines and tissues and found that target repertoires were largely unaffected, with secondary effects explaining most of the differential responses detected. Outliers resulting from differential direct targeting were often attributable to alternative 3′ UTR isoform usage that modulated the presence of miRNA sites. More inclusive examination of alternative 3′ UTR isoforms revealed that they influence ~10% of predicted targets when comparing any two cell types. Indeed, considering alternative 3′ UTR isoform usage improved prediction of targeting efficacy significantly beyond the improvements observed when considering constitutive isoform usage. Thus, although miRNA targeting is remarkably consistent in different cell types, considering the 3′ UTR landscape helps predict targeting efficacy and explain differential regulation that is observed. Korea (South). Ministry of Education, Science and Technology (MEST) (National Research Foundation of Korea. NRF-2013R1A1A1010185) National Institutes of Health (U.S.) (Grant RO1 GM067031) National Institutes of Health (U.S.) (Grant K99 GM102319) National Science Foundation (U.S.). Graduate Research Fellowship Program 2015-04-02T16:13:11Z 2015-04-02T16:13:11Z 2014-03 2014-01 Article http://purl.org/eprint/type/JournalArticle 10972765 1097-4164 http://hdl.handle.net/1721.1/96328 Nam, Jin-Wu, Olivia S. Rissland, David Koppstein, Cei Abreu-Goodger, Calvin H. Jan, Vikram Agarwal, Muhammed A. Yildirim, Antony Rodriguez, and David P. Bartel. “Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting.” Molecular Cell 53, no. 6 (March 2014): 1031–1043. © 2014 Elsevier Inc. https://orcid.org/0000-0002-3872-2856 en_US http://dx.doi.org/10.1016/j.molcel.2014.02.013 Molecular Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier Open Archive |
| spellingShingle | Nam, Jin-Wu Rissland, Olivia S. Abreu-Goodger, Cei Jan, Calvin H. Agarwal, Vikram Yildirim, Muhammed A. Rodriguez, Antony Koppstein, David Neal Pira Bartel, David Rissland, Olivia S. Jan, Calvin H. Yildirim, Muhammed A. Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting |
| title | Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting |
| title_full | Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting |
| title_fullStr | Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting |
| title_full_unstemmed | Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting |
| title_short | Global Analyses of the Effect of Different Cellular Contexts on MicroRNA Targeting |
| title_sort | global analyses of the effect of different cellular contexts on microrna targeting |
| url | http://hdl.handle.net/1721.1/96328 https://orcid.org/0000-0002-3872-2856 |
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