1. Academic Validation
  2. Differential hepatitis C virus RNA target site selection and host factor activities of naturally occurring miR-122 3΄ variants

Differential hepatitis C virus RNA target site selection and host factor activities of naturally occurring miR-122 3΄ variants

  • Nucleic Acids Res. 2017 May 5;45(8):4743-4755. doi: 10.1093/nar/gkw1332.
Daisuke Yamane 1 2 Sara R Selitsky 1 3 4 Tetsuro Shimakami 1 5 You Li 1 2 Mi Zhou 1 3 4 Masao Honda 5 Praveen Sethupathy 1 3 4 Stanley M Lemon 1 2
Affiliations

Affiliations

  • 1 Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 2 Departments of Medicine and Microbiology & Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7292, USA.
  • 3 Bioinformatics and Computational Biology Curriculum, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 4 Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
  • 5 Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa 920-8641, Japan.
Abstract

In addition to suppressing cellular gene expression, certain miRNAs potently facilitate replication of specific positive-strand RNA viruses. miR-122, a pro-viral hepatitis C virus (HCV) host factor, binds and recruits Ago2 to tandem sites (S1 and S2) near the 5΄ end of the HCV genome, stabilizing it and promoting its synthesis. HCV target site selection follows canonical miRNA rules, but how non-templated 3΄ miR-122 modifications impact this unconventional miRNA action is unknown. High-throughput Sequencing revealed that a 22 nt miRNA with 3΄G ('22-3΄G') comprised <63% of total miR-122 in human liver, whereas other variants (23-3΄A, 23-3΄U, 21-3΄U) represented 11-17%. All loaded equivalently into Ago2, and when tested individually functioned comparably in suppressing gene expression. In contrast, 23-3΄A and 23-3΄U were more active than 22-3΄G in stabilizing HCV RNA and promoting its replication, whereas 21-3΄U was almost completely inactive. This lack of 21-3΄U HCV host factor activity correlated with reduced recruitment of Ago2 to the HCV S1 site. Additional experiments demonstrated strong preference for guanosine at nt 22 of miR-122. Our findings reveal the importance of non-templated 3΄ miR-122 modifications to its HCV host factor activity, and identify unexpected differences in miRNA requirements for host gene suppression versus RNA virus replication.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-15005
    99.97%, HCV 抑制剂
    HCV