Selective degradation of host MicroRNAs by an intergenic HCMV noncoding RNA accelerates virus production

Sanghyun Lee1, Jaewon Song, Sungchul Kim

  • 1National Creative Research Initiatives Center for Antigen Presentation, Seoul 151-747, Republic of Korea.

Cell Host & Microbe
|June 18, 2013
PubMed

Insights

Human cytomegalovirus (HCMV) uses a viral RNA element to degrade specific host microRNAs (miRNAs), enhancing viral replication. This discovery reveals a novel mechanism of viral pathogenesis involving noncoding RNA regulation.

Area of Science:

  • Virology
  • Molecular Biology
  • RNA Biology

Background:

  • Human cytomegalovirus (HCMV) virulence is linked to a specific genomic segment.
  • The mechanism by which this segment influences virulence is not well understood.

Purpose of the Study:

  • To investigate the function of a 15 kb segment in HCMV virulence.
  • To elucidate the role of viral noncoding RNA in regulating host microRNAs.

Main Methods:

  • Analysis of intergenic RNA sequences within the HCMV 15 kb segment.
  • Investigating the interaction between viral RNA and host microRNAs (miRNAs).
  • Assessing the impact of these interactions on viral production during lytic infection.

Main Results:

  • Viral RNA sequences function as miRNA decay elements (miRDEs), selectively degrading mature miR-17 and miR-20a.
  • Mutations in miRNA binding sites altered miRDE targeting to other cluster miRNAs.
  • miRDE activity was essential for accelerated virus production in lytic HCMV infection.

Conclusions:

  • Viral noncoding RNA regulates cellular miRNAs during HCMV infection.
  • Noncoding RNAs may play a significant role in the turnover of mature miRNAs.
  • This interaction contributes to HCMV pathogenesis and virulence.

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