Viral miRNA adaptor differentially recruits miRNAs to target mRNAs through alternative base-pairing

  1. Carlos Gorbea
  2. Tim Mosbruger
  3. David A Nix
  4. Demián Cazalla  Is a corresponding author
  1. University of Utah School of Medicine, United States
  2. 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.

The following data sets were generated

Article and author information

Author details

  1. Carlos Gorbea

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Tim Mosbruger

    Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. David A Nix

    Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Demián Cazalla

    Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, United States
    For correspondence
    dcazalla@biochem.utah.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9076-3655

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.

Reviewing Editor

  1. Timothy W Nilsen, Case Western Reserve University, United States

Version history

  1. Received: July 25, 2019
  2. Accepted: September 19, 2019
  3. Accepted Manuscript published: September 20, 2019 (version 1)
  4. Version of Record published: September 26, 2019 (version 2)

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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  1. Carlos Gorbea
  2. Tim Mosbruger
  3. David A Nix
  4. Demián Cazalla
(2019)
Viral miRNA adaptor differentially recruits miRNAs to target mRNAs through alternative base-pairing
eLife 8:e50530.
https://doi.org/10.7554/eLife.50530

Share this article

https://doi.org/10.7554/eLife.50530

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