An unbiased proteomics approach to identify human cytomegalovirus RNA-associated proteins

Virology. 2015 Jul:481:13-23. doi: 10.1016/j.virol.2015.02.008. Epub 2015 Mar 9.

Abstract

Post-transcriptional events regulate herpesvirus gene expression, yet few herpesvirus RNA-binding proteins have been identified. We used an unbiased approach coupling oligo(dT) affinity capture with proteomics to identify viral RNA-associated proteins during infection. Using this approach, we identified and confirmed changes in the abundance or activity of two host RNA-associated proteins, DHX9 and DDX3, in cells infected with human cytomegalovirus (HCMV). We also identified and confirmed previously unreported activities for the HCMV US22 and pp71 proteins as RNA-associated viral proteins and confirmed that a known viral RNA-binding protein, pTRS1, associates with RNA in infected cells. Further, we found that HCMV pp71 co-sedimented with polysomes, associated with host and viral RNAs, and stimulated the overall rate of protein synthesis. These results demonstrate that oligo(dT) affinity capture coupled with proteomics provides a rapid and straightforward means to identify RNA-associated viral proteins during infection that may participate in the post-transcriptional control of gene expression.

Keywords: Herpesvirus; Human cytomegalovirus (HCMV); Messenger RNA (mRNA); Post-transcriptional regulation; Proteomics; RNA-binding; Translation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytomegalovirus / genetics
  • Cytomegalovirus / metabolism
  • Cytomegalovirus Infections / genetics
  • Cytomegalovirus Infections / metabolism*
  • Cytomegalovirus Infections / virology
  • Humans
  • Molecular Sequence Data
  • Protein Biosynthesis
  • Proteomics*
  • RNA, Viral / genetics
  • RNA, Viral / metabolism*
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*

Substances

  • RNA, Viral
  • RNA-Binding Proteins