Effect of tRNA on the Maturation of HIV-1 Reverse Transcriptase

J Mol Biol. 2018 Jun 22;430(13):1891-1900. doi: 10.1016/j.jmb.2018.02.027. Epub 2018 May 8.


The mature HIV-1 reverse transcriptase is a heterodimer that comprises 66 kDa (p66) and 51 kDa (p51) subunits. The latter is formed by HIV-1 protease-catalyzed removal of a C-terminal ribonuclease H domain from a p66 subunit. This proteolytic processing is a critical step in virus maturation and essential for viral infectivity. Here, we report that tRNA significantly enhances in vitro processing even at a substoichiometric tRNA:p66/p66 ratio. Other double-stranded RNAs have considerably less pronounced effect. Our data support a model where interaction of p66/p66 with tRNA introduces conformational asymmetry in the two subunits, permitting specific proteolytic processing of one p66 to provide the mature RT p66/p51 heterodimer.

Keywords: HIV-1; RNase H; maturation; proteolysis; reverse transcriptase; tRNA.

Publication types

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

MeSH terms

  • HIV Reverse Transcriptase / chemistry
  • HIV Reverse Transcriptase / metabolism*
  • HIV-1 / enzymology*
  • HIV-1 / genetics
  • Models, Molecular
  • Protein Conformation
  • Protein Multimerization
  • Proteolysis
  • RNA, Transfer / metabolism*
  • RNA, Viral / metabolism
  • Ribonuclease H / metabolism


  • RNA, Viral
  • RNA, Transfer
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase
  • Ribonuclease H