2026-09-19T18:49:18Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/1218772026-06-17T14:44:51Zcom_1721.1_7582com_1721.1_7581col_1721.1_131022
Christopher B. Burge.
Cherone, Jennifer M.(Jennifer Michelle)
Massachusetts Institute of Technology. Department of Biology.
Massachusetts Institute of Technology. Department of Biology
2019-07-22T19:33:00Z
2019-07-22T19:33:00Z
2019
2019
https://hdl.handle.net/1721.1/121877
1102636747
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2019
Cataloged from PDF version of thesis. Vita.
Includes bibliographical references.
MicroRNAs (miRNAs) play roles in diverse developmental processes and cellular differentiation. Distinct miRNAs have hundreds to thousands of conserved binding sites in mRNAs, but typically exert only modest repression on a single site. Co-targeting of individual mRNAs by multiple different miRNAs could be commonly used to achieve stronger and more complex patterns of repression. Comparing target sets of different miRNAs, we identified hundreds of pairs of miRNAs that share more mRNA targets than expected (often ~2-fold or more) relative to stringent controls. For one co-targeting pair, miR-138 and miR-137, we validated functional overlap in neuronal differentiation. Clustering of the pairing relationships revealed a group of 9 predominantly brain-enriched miRNAs that share many targets. In reporter assays, subsets of these miRNAs together repressed gene expression by 5- to 10-fold or more, sometimes exhibiting cooperative repression. Our results uncover an unexpected pattern in which certain combinations of miRNAs can collaborate to strongly repress particular targets, and suggest important developmental roles.
by Jennifer M. Cherone.
Ph.D.
Ph.D. Massachusetts Institute of Technology, Department of Biology
130 pages
eng
Massachusetts Institute of Technology
MIT theses are protected by copyright. They may be viewed, downloaded, or printed from this source but further reproduction or distribution in any format is prohibited without written permission.
http://dspace.mit.edu/handle/1721.1/7582
Biology.
Co-targeting among microRNAs is widespread and enriched in the brain
Thesis
application/pdf
2019-07-22T19:32:55Z
Publication
Doctoral
Bio
unknown
unknown
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<Abstract>MicroRNAs (miRNAs) play roles in diverse developmental processes and cellular differentiation. Distinct miRNAs have hundreds to thousands of conserved binding sites in mRNAs, but typically exert only modest repression on a single site. Co-targeting of individual mRNAs by multiple different miRNAs could be commonly used to achieve stronger and more complex patterns of repression. Comparing target sets of different miRNAs, we identified hundreds of pairs of miRNAs that share more mRNA targets than expected (often ~2-fold or more) relative to stringent controls. For one co-targeting pair, miR-138 and miR-137, we validated functional overlap in neuronal differentiation. Clustering of the pairing relationships revealed a group of 9 predominantly brain-enriched miRNAs that share many targets. In reporter assays, subsets of these miRNAs together repressed gene expression by 5- to 10-fold or more, sometimes exhibiting cooperative repression. Our results uncover an unexpected pattern in which certain combinations of miRNAs can collaborate to strongly repress particular targets, and suggest important developmental roles.</Abstract>
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