Viral miRNA adaptor differentially recruits miRNAs to target mRNAs through alternative base-pairing
- University of Utah School of Medicine, United States
- Children's Hospital of Philadelphia, United States
Abstract
HSUR2 is a viral non-coding RNA (ncRNA) that functions as a microRNA (miRNA) adaptor. HSUR2 inhibits apoptosis in infected cells by recruiting host miRNAs miR-142-3p and miR-16 to mRNAs encoding apoptotic factors. HSUR2's target recognition mechanism is not understood. It is also unknown why HSUR2 utilizes miR-16 to downregulate only a subset of transcripts. We developed a general method for individual-nucleotide resolution RNA-RNA interaction identification by crosslinking and capture (iRICC) to identify sequences mediating interactions between HSUR2 and target mRNAs in vivo. Mutational analyses confirmed identified HSUR2-mRNA interactions and validated iRICC as a method that confidently determines sequences mediating RNA-RNA interactions in vivo. We show that HSUR2 does not display a 'seed' region to base-pair with most target mRNAs, but instead uses different regions to interact with different transcripts. We further demonstrate that this versatile mode of interaction via variable base-pairing provides HSUR2 with a mechanism for differential miRNA recruitment.
Data availability
The described RNA-seq data have been deposited in the Gene Expression Omnibus under the accession number GSE125371.
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Viral miRNA adaptor differentially recruits miRNAs to target mRNAs through alternative base-pairingNCBI Gene Expression Omnibus, GSE125371.
Article and author information
Author details
Funding
National Institute of General Medical Sciences (RO1-GM118829)
- Demián Cazalla
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Gorbea et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Viral miRNA adaptor differentially recruits miRNAs to target mRNAs through alternative base-pairing
eLife 8:e50530.
https://doi.org/10.7554/eLife.50530
