PABP1 Drives the Selective Translation of Influenza A Virus mRNA

J Mol Biol. 2022 Mar 15;434(5):167460. doi: 10.1016/j.jmb.2022.167460. Epub 2022 Jan 21.

Abstract

Influenza A virus (IAV) is a human-infecting pathogen with a history of causing seasonal epidemics and on several occasions worldwide pandemics. Infection by IAV causes a dramatic decrease in host mRNA translation, whereas viral mRNAs are efficiently translated. The IAV mRNAs have a highly conserved 5'-untranslated region (5'UTR) that is rich in adenosine residues. We show that the human polyadenylate binding protein 1 (PABP1) binds to the 5'UTR of the viral mRNAs. The interaction of PABP1 with the viral 5'UTR makes the translation of viral mRNAs more resistant to canonical cap-dependent translation inhibition than model mRNAs. Additionally, PABP1 bound to the viral 5'UTR can recruit eIF4G in an eIF4E-independent manner. These results indicate that PABP1 bound to the viral 5'UTR may promote eIF4E-independent translation initiation.

Keywords: RT-qPCR; anisotropy; eukaryotic initiation factor 4G; immunoprecipitation; poly(A) binding protein.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • 5' Untranslated Regions / genetics
  • Eukaryotic Initiation Factor-4E / metabolism
  • Eukaryotic Initiation Factor-4G / metabolism
  • Humans
  • Influenza A virus* / genetics
  • Influenza A virus* / metabolism
  • Poly(A)-Binding Protein I* / genetics
  • Poly(A)-Binding Protein I* / metabolism
  • Protein Biosynthesis
  • RNA, Messenger* / genetics
  • RNA, Messenger* / metabolism
  • RNA, Viral* / genetics
  • RNA, Viral* / metabolism

Substances

  • 5' Untranslated Regions
  • Eukaryotic Initiation Factor-4E
  • Eukaryotic Initiation Factor-4G
  • Poly(A)-Binding Protein I
  • RNA, Messenger
  • RNA, Viral