Co-targeting among microRNAs is widespread and enriched in the brain
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1102636747-MIT.pdf
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9.81 MB
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Adobe PDF
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33314530ae399eb7a3b34f2798fcb129
Author(s)
Cherone, Jennifer M.(Jennifer Michelle)
Advisor(s)
Christopher B. Burge.
Date Issued
2019
Publisher
Massachusetts Institute of Technology
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.
Description
Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biology, 2019
Cataloged from PDF version of thesis. Vita.
Includes bibliographical references.
Subjects
Biology.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
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