MicroRNA 3′-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position
Name
elife-69803-v2.pdf
Description
Published version
Size
1.9 MB
Format
Adobe PDF
Checksum (MD5)
6ea1b2703fc50dee64b15ed89e81cd80
Author(s)
McGeary, Sean E
Bisaria, Namita
Pham, Thy M
Wang, Peter Y
Bartel, David P
Date Issued
2022
Journal
eLife
Publisher
eLife Sciences Publications, Ltd
Citation
McGeary, Sean E, Bisaria, Namita, Pham, Thy M, Wang, Peter Y and Bartel, David P. 2022. "MicroRNA 3′-compensatory pairing occurs through two binding modes, with affinity shaped by nucleotide identity and position." eLife, 11.
Version
Final published version
Abstract
MicroRNAs (miRNAs), in association with Argonaute (AGO) proteins, direct repression by pairing to sites within mRNAs. Compared to pairing preferences of the miRNA seed region (nucleotides 2–8), preferences of the miRNA 3′ region are poorly understood, due to the sparsity of measured affinities for the many pairing possibilities. We used RNA bind-n-seq with purified AGO2–miRNA complexes to measure relative affinities of >1000 3′-pairing architectures for each miRNA. In some cases, optimal 3′ pairing increased affinity by >500 fold. Some miRNAs had two high-affinity 3′-pairing modes—one of which included additional nucleotides bridging seed and 3′ pairing to enable high-affinity pairing to miRNA nucleotide 11. The affinity of binding and the position of optimal pairing both tracked with the occurrence of G or oligo(G/C) nucleotides within the miRNA. These and other results advance understanding of miRNA targeting, providing insight into how optimal 3′ pairing is determined for each miRNA.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
Howard Hughes Medical Institute
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.7554/ELIFE.69803
