Unc-13 homolog D mediates an antiviral effect of the chromosome 19 microRNA cluster miR-517a.

Journal Article (Journal Article)

The function of microRNAs (miRNAs) can be cell autonomous or communicated to other cell types and has been implicated in diverse biological processes. We previously demonstrated that miR-517a-3p (miR-517a), a highly expressed member of the chromosome 19 miRNA cluster (C19MC) that is transcribed almost exclusively in human trophoblasts, attenuates viral replication via induction of autophagy in non-trophoblastic recipient cells. However, the molecular mechanisms underlying these effects remain unknown. Here, we identified unc-13 homolog D (UNC13D) as a direct, autophagy-related gene target of miR-517a, leading to repression of UNC13D. In line with the antiviral activity of miR-517a, silencing UNC13D suppressed replication of vesicular stomatitis virus (VSV), whereas overexpression of UNC13D increased VSV levels, suggesting a role for UNC13D silencing in the antiviral activity of miR-517a. We also found that miR-517a activated NF-κB signaling in HEK-293XL cells expressing TLR8, but the effect was not specific to C19MC miRNA. Taken together, our results define mechanistic pathways that link C19MC miRNA with inhibition of viral replication.

Full Text

Duke Authors

Cited Authors

  • Krawczynski, K; Ouyang, Y; Mouillet, J-F; Chu, T; Coyne, CB; Sadovsky, Y

Published Date

  • November 19, 2020

Published In

Volume / Issue

  • 134 / 5

PubMed ID

  • 33093239

Pubmed Central ID

  • PMC7687871

Electronic International Standard Serial Number (EISSN)

  • 1477-9137

Digital Object Identifier (DOI)

  • 10.1242/jcs.246769

Language

  • eng

Conference Location

  • England