Co-targeting among microRNAs is widespread and enriched in the brain

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.

Name thesis:degree_name

Doctoral

Department dc:contributor.department

Massachusetts Institute of Technology. Department of Biology

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2019

Author dc:creator

• Cherone, Jennifer M.(Jennifer Michelle)

Advisor dc:contributor.advisor

• Christopher B. Burge.

• Biology.

Statement dc:rights

• 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.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

https://hdl.handle.net/1721.1/121877

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/121877