The P body protein LSm1 contributes to stimulation of hepatitis C virus translation, but not replication, by

Ashley P E Roberts1, Rachel Doidge, Alexander W Tarr

  • 1School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK.

Nucleic Acids Research
|October 22, 2013
PubMed

Insights

The P body protein LSm1 specifically activates hepatitis C virus (HCV) translation mediated by microRNA-122 (miR-122). LSm1

Area of Science:

  • Virology
  • Molecular Biology
  • RNA Biology

Background:

  • Hepatitis C virus (HCV) replication relies on liver-specific microRNA-122 (miR-122).
  • P body protein LSm1 is known to stimulate HCV translation and replication.
  • miR-122 is associated with P bodies, suggesting a potential link with LSm1.

Purpose of the Study:

  • To investigate the role of LSm1 in miR-122-mediated regulation of HCV.
  • To determine if LSm1 specifically influences miR-122's effects on HCV translation and replication.

Main Methods:

  • Investigated LSm1's effect on HCV internal ribosome entry site (IRES)-driven translation.
  • Assessed LSm1's impact on miR-122's repressive function and cleavage activity.
  • Examined LSm1's influence on microRNA-induced silencing complex recruitment.
  • Compared LSm1's requirement for miR-122 in HCV translation versus replication.

Main Results:

  • LSm1 specifically activates miR-122-mediated HCV IRES-driven translation.
  • LSm1 depletion did not affect miR-122's repressive function or cleavage activity.
  • LSm1 does not influence microRNA-induced silencing complex recruitment to the HCV 5'UTR.
  • LSm1 is not required for miR-122 to stimulate HCV replication, indicating distinct regulatory mechanisms.

Conclusions:

  • LSm1 is a novel protein factor specifically involved in activating HCV IRES-driven translation by miR-122.
  • LSm1's role in miR-122 function is specific to translation activation, not other miRNA activities.
  • miR-122 regulation of HCV translation and replication by LSm1 involves different requirements.

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