miR-122 and Ago interactions with the HCV genome alter the structure of the viral 5' terminus

Jasmin Chahal, Luca F.R. Gebert, Hin Hark Gan, Edna Camacho, Kristin Gunsalus, Ian J. MacRae, Selena M. Sagan

Research output: Contribution to journalArticle

Abstract

Hepatitis C virus (HCV) is a positive-sense RNA virus that interacts with the liver-specific microRNA, miR-122. miR-122 binds to two sites in the 5' untranslated region (UTR) and this interaction promotes HCV RNA accumulation, although the precise role of miR-122 in the HCV life cycle remains unclear. Using biophysical analyses and Selective 2' Hydroxyl Acylation analyzed by Primer Extension (SHAPE) we investigated miR-122 interactions with the 5' UTR. Our data suggests that miR-122 binding results in alteration of nucleotides 1-117 to suppress an alternative secondary structure and promote functional internal ribosomal entry site (IRES) formation. Furthermore, we demonstrate that two hAgo2:miR-122 complexes are able to bind to the HCV 5' terminus simultaneously and SHAPE analyses revealed further alterations to the structure of the 5' UTR to accommodate these complexes. Finally, we present a computational model of the hAgo2:miR-122:HCV RNA complex at the 5' terminus of the viral genome as well as hAgo2:miR-122 interactions with the IRES-40S complex that suggest hAgo2 is likely to form additional interactions with SLII which may further stabilize the HCV IRES. Taken together, our results support a model whereby hAgo2:miR-122 complexes alter the structure of the viral 5' terminus and promote formation of the HCV IRES.

Original languageEnglish (US)
Pages (from-to)5307-5324
Number of pages18
JournalNucleic acids research
Volume47
Issue number10
DOIs
StatePublished - Jun 4 2019

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Viral Structures
Hepacivirus
Genome
5' Untranslated Regions
Acylation
Hydroxyl Radical
RNA
Viral Genome
RNA Viruses
Life Cycle Stages
MicroRNAs
Nucleotides
Liver

ASJC Scopus subject areas

  • Genetics

Cite this

Chahal, J., Gebert, L. F. R., Gan, H. H., Camacho, E., Gunsalus, K., MacRae, I. J., & Sagan, S. M. (2019). miR-122 and Ago interactions with the HCV genome alter the structure of the viral 5' terminus. Nucleic acids research, 47(10), 5307-5324. https://doi.org/10.1093/nar/gkz194

miR-122 and Ago interactions with the HCV genome alter the structure of the viral 5' terminus. / Chahal, Jasmin; Gebert, Luca F.R.; Gan, Hin Hark; Camacho, Edna; Gunsalus, Kristin; MacRae, Ian J.; Sagan, Selena M.

In: Nucleic acids research, Vol. 47, No. 10, 04.06.2019, p. 5307-5324.

Research output: Contribution to journalArticle

Chahal, J, Gebert, LFR, Gan, HH, Camacho, E, Gunsalus, K, MacRae, IJ & Sagan, SM 2019, 'miR-122 and Ago interactions with the HCV genome alter the structure of the viral 5' terminus', Nucleic acids research, vol. 47, no. 10, pp. 5307-5324. https://doi.org/10.1093/nar/gkz194
Chahal, Jasmin ; Gebert, Luca F.R. ; Gan, Hin Hark ; Camacho, Edna ; Gunsalus, Kristin ; MacRae, Ian J. ; Sagan, Selena M. / miR-122 and Ago interactions with the HCV genome alter the structure of the viral 5' terminus. In: Nucleic acids research. 2019 ; Vol. 47, No. 10. pp. 5307-5324.
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