Ribonuclease H: properties, substrate specificity and roles in retroviral reverse transcription

• Published in: The FEBS journal Vol. 276; no. 6; pp. 1506 - 1516
• Main Authors: Champoux, James J, Schultz, Sharon J
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.03.2009; Blackwell Publishing Ltd
• Subjects: Biocatalysis; Biochemistry; catalytic mechanism; DNA polymerase; DNA/RNA hybrids; endonuclease; Genomics; human immunodeficiency virus, type 1; Models, Molecular; Moloney murine leukemia virus; Murine leukemia virus; polypurine tract; Protein Conformation; Retroviridae - enzymology; reverse transcriptase; reverse transcription; Ribonuclease H - chemistry; Ribonuclease H - metabolism; RNA cleavage; RNA-directed DNA polymerase; RNase H; Structure-Activity Relationship; Substrate Specificity; Substrates; Transcription, Genetic; Viruses
• ISSN: 1742-464X; 1742-4658
• DOI: 10.1111/j.1742-4658.2009.06909.x

Retroviral reverse transcriptases possess both a DNA polymerase and an RNase H activity. The linkage with the DNA polymerase activity endows the retroviral RNases H with unique properties not found in the cellular counterparts. In addition to the typical endonuclease activity on a DNA/RNA hybrid, cleavage by the retroviral enzymes is also directed by both DNA 3' recessed and RNA 5' recessed ends, and by certain nucleotide sequence preferences in the vicinity of the cleavage site. This spectrum of specificities enables retroviral RNases H to carry out a series of cleavage reactions during reverse transcription that degrade the viral RNA genome after minus-strand synthesis, precisely generate the primer for the initiation of plus strands, facilitate the initiation of plus-strand synthesis and remove both plus- and minus-strand primers after they have been extended.