The biochemical basis of microRNA targeting efficacy
Name
nihms-1065638.pdf
Description
Accepted version
Size
3.05 MB
Format
Adobe PDF
Checksum (MD5)
b0388096edd0839c38cb06e81c5f5b25
Author(s)
McGeary, Sean E
Lin, Kathy S
Shi, Charlie Y
Pham, Thy M
Bisaria, Namita
Kelley, Gina M
Bartel, David P
Date Issued
2019
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Version
Author's final manuscript
Abstract
© 2019 American Association for the Advancement of Science. All rights reserved. MicroRNAs (miRNAs) act within Argonaute proteins to guide repression of messenger RNA targets. Although various approaches have provided insight into target recognition, the sparsity of miRNA-target affinity measurements has limited understanding and prediction of targeting efficacy. Here, we adapted RNA bind-n-seq to enable measurement of relative binding affinities between Argonaute-miRNA complexes and all sequences ≤12 nucleotides in length. This approach revealed noncanonical target sites specific to each miRNA, miRNA-specific differences in canonical target-site affinities, and a 100-fold impact of dinucleotides flanking each site. These data enabled construction of a biochemical model of miRNA-mediated repression, which was extended to all miRNA sequences using a convolutional neural network. This model substantially improved prediction of cellular repression, thereby providing a biochemical basis for quantitatively integrating miRNAs into gene-regulatory networks.
MIT Department
Howard Hughes Medical Institute
Whitehead Institute for Biomedical Research
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Computational and Systems Biology Program
Terms of Use
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.
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1126/SCIENCE.AAV1741
