Sequestration of microRNA-mediated target repression by the Ago2-associated RNA-binding protein FAM120A
Name
RNA-2019-Kelly-1291-7.pdf
Description
Published version
Size
1.06 MB
Format
Adobe PDF
Checksum (MD5)
eb1d88adf69d9ff037f4140c65d912e1
Author(s)
Kelly, Timothy J.
Suzuki, Hiroshi I.
Zamudio, Jesse R.
Suzuki, Megumu
Date Issued
July 9, 2019
Journal
RNA
Publisher
Cold Spring Harbor Laboratory Press
Citation
Kelly, Timothy J. et al. "Sequestration of microRNA-mediated target repression by the Ago2-associated RNA-binding protein FAM120A." RNA 25 (2019):1291-1297 © 2019 The Author(s)
Version
Final published version
Abstract
Argonaute (Ago) proteins interact with various binding partners and play a pivotal role in microRNA (miRNA)-mediated silencing pathways. By utilizing immunoprecipitation followed by mass spectrometry to determine cytoplasmic Ago2 protein complexes in mouse embryonic stem cells (mESCs), we identified a putative RNA-binding protein FAM120A (also known as OSSA/C9ORF10) as an Ago2 interacting protein. Individual nucleotide resolution cross-linking and immunoprecipitation (iCLIP) analysis revealed that FAM120A binds to homopolymeric tracts in 3′′-UTRs of about 2000 mRNAs, particularly poly(G) sequences. Comparison of FAM120A iCLIP and Ago2 iCLIP reveals that greater than one-third of mRNAs bound by Ago2 in mESCs are co-bound by FAM120A. Furthermore, such FAM120A-bound Ago2 target genes are not subject to Ago2-mediated target degradation. Reporter assays suggest that the 3′′-UTRs of several FAM120A-bound miRNA target genes are less sensitive to Ago2-mediated target repression than those of FAM120A-unbound miRNA targets and FAM120A modulates them via its G-rich target sites. These findings suggest that Ago2 may exist in multiple protein complexes with varying degrees of functionality.
Subjects
Molecular Biology
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution NonCommercial License 4.0
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1261/rna.071621.119
