RNA–RNA interactions between respiratory syncytial virus and miR-26 and miR-27 are associated with regulation of cell cycle and antiviral immunity

Sarah Ressel, Sujai Kumar, Jose Roberto Bermúdez-Barrientos, Katrina Gordon, Julia Lane, Jin Wu, Cei Abreu-Goodger, Jürgen Schwarze, Amy H. Buck*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

microRNAs (miRNAs) regulate nearly all physiological processes but our understanding of exactly how they function remains incomplete, particularly in the context of viral infections. Here, we adapt a biochemical method (CLEAR-CLIP) and analysis pipeline to identify targets of miRNAs in lung cells infected with Respiratory syncytial virus (RSV). We show that RSV binds directly to miR-26 and miR-27 through seed pairing and demonstrate that these miRNAs target distinct gene networks associated with cell cycle and metabolism (miR-27) and antiviral immunity (miR-26). Many of the targets are de-repressed upon infection and we show that the miR-27 targets most sensitive to miRNA inhibition are those associated with cell cycle. Finally, we demonstrate that high confidence chimeras map to long noncoding RNAs (lncRNAs) and pseudogenes in transcriptional regulatory regions. We validate that a proportion of miR-27 and Argonaute 2 (AGO2) is nuclear and identify a long non-coding RNA (lncRNA) as a miR-27 target that is linked to transcriptional regulation of nearby genes. This work expands the target networks of miR-26 and miR-27 to include direct interactions with RSV and lncRNAs and implicate these miRNAs in regulation of key genes that impact the viral life cycle associated with cell cycle, metabolism, and antiviral immunity.
Original languageEnglish
Pages (from-to)4872-4888
Number of pages17
JournalNucleic Acids Research
Volume52
Issue number9
Early online date27 Feb 2024
DOIs
Publication statusPublished - 22 May 2024

Fingerprint

Dive into the research topics of 'RNA–RNA interactions between respiratory syncytial virus and miR-26 and miR-27 are associated with regulation of cell cycle and antiviral immunity'. Together they form a unique fingerprint.

Cite this