retroviral ribonuclease H;
RT/RNase H;
retroviral reverse transcriptase RNaseH;
HIV RNase H

Hydrolases;
Acting on ester bonds;
Endoribonucleases producing 5'-phosphomonoesters

Endohydrolysis of RNA in RNA/DNA hybrids. Three different cleavage modes 1. sequence-specific internal cleavage of RNA [1-4]. Human immunodeficiency virus type 1 and Moloney murine leukemia virus enzymes prefer to cleave the RNA strand one nucleotide away from the RNA-DNA junction [5] 2. RNA 5'-end directed cleavage 13-19 nucleotides from the RNA end [6,7] 3. DNA 3'-end directed cleavage 15-20 nucleotides away from the primer terminus [8-10].

Comments: Retroviral reverse transcriptase is a multifunctional enzyme responsible for viral replication. To perform this task the enzyme combines two distinct activities. The polymerase domain (EC 2.7.7.49, RNA-directed DNA polymerase) occupies the N-terminal two-thirds of the reverse transcriptase whereas the ribonuclease H domain comprises the C-terminal remaining one-third [13,14]. The RNase H domain of Moloney murine leukemia virus and Human immunodeficiency virus display two metal binding sites [15-17]

1  [PMID:15533434]

Schultz SJ, Zhang M, Champoux JJ

Recognition of internal cleavage sites by retroviral RNases H.

J. Mol. Biol. 344 (2004) 635-52.

2  [PMID:11250910]

Sarafianos SG, Das K, Tantillo C, Clark AD Jr, Ding J, Whitcomb JM, Boyer PL, Hughes SH, Arnold E

Crystal structure of HIV-1 reverse transcriptase in complex with a polypurine tract RNA:DNA.

EMBO. J. 20 (2001) 1449-61.

3  [PMID:11939780]

Rausch JW, Lener D, Miller JT, Julias JG, Hughes SH, Le Grice SF

Altering the RNase H primer grip of human immunodeficiency virus reverse transcriptase modifies cleavage specificity.

Biochemistry. 41 (2002) 4856-65.

4  [PMID:19067547]

Brehm JH, Mellors JW, Sluis-Cremer N

Mechanism by which a glutamine to leucine substitution at residue 509 in the ribonuclease H domain of HIV-1 reverse transcriptase confers zidovudine resistance.

Biochemistry. 47 (2008) 14020-7.

5  [PMID:10913435]

Schultz SJ, Zhang M, Kelleher CD, Champoux JJ

Analysis of plus-strand primer selection, removal, and reutilization by retroviral reverse transcriptases.

J. Biol. Chem. 275 (2000) 32299-309.

6  [PMID:7692401]

DeStefano JJ, Mallaber LM, Fay PJ, Bambara RA

Determinants of the RNase H cleavage specificity of human immunodeficiency virus  reverse transcriptase.

Nucleic. Acids. Res. 21 (1993) 4330-8.

7  [PMID:1281479]

Kati WM, Johnson KA, Jerva LF, Anderson KS

Mechanism and fidelity of HIV reverse transcriptase.

J. Biol. Chem. 267 (1992) 25988-97.

8  [PMID:8567660]

Palaniappan C, Fuentes GM, Rodriguez-Rodriguez L, Fay PJ, Bambara RA

Helix structure and ends of RNA/DNA hybrids direct the cleavage specificity of HIV-1 reverse transcriptase RNase H.

J. Biol. Chem. 271 (1996) 2063-70.

9  [PMID:1376369]

Fu TB, Taylor J

When retroviral reverse transcriptases reach the end of their RNA templates.

J. Virol. 66 (1992) 4271-8.

10 [PMID:19289131]

Beilhartz GL, Wendeler M, Baichoo N, Rausch J, Le Grice S, Gotte M

HIV-1 reverse transcriptase can simultaneously engage its DNA/RNA substrate at both DNA polymerase and RNase H active sites: implications for RNase H inhibition.

J. Mol. Biol. 388 (2009) 462-74.

11 [PMID:9831551]

Huang H, Chopra R, Verdine GL, Harrison SC

Structure of a covalently trapped catalytic complex of HIV-1 reverse transcriptase: implications for drug resistance.

Science. 282 (1998) 1669-75.

12 [PMID:2471188]

Krug MS, Berger SL

Ribonuclease H activities associated with viral reverse transcriptases are endonucleases.

Proc. Natl. Acad. Sci. U. S. A. 86 (1989) 3539-43.

13 [PMID:19228195]

Champoux JJ, Schultz SJ

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

FEBS. J. 276 (2009) 1506-16.

14 [PMID:18261820]

Schultz SJ, Champoux JJ

RNase H activity: structure, specificity, and function in reverse transcription.

Virus. Res. 134 (2008) 86-103.

15 [PMID:10585503]

Goedken ER, Marqusee S

Metal binding and activation of the ribonuclease H domain from moloney murine leukemia virus.

Protein. Eng. 12 (1999) 975-80.

16 [PMID:1707186]

Davies JF 2nd, Hostomska Z, Hostomsky Z, Jordan SR, Matthews DA

Crystal structure of the ribonuclease H domain of HIV-1 reverse transcriptase.

Science. 252 (1991) 88-95.

17 [PMID:12534276]

Pari K, Mueller GA, DeRose EF, Kirby TW, London RE

Solution structure of the RNase H domain of the HIV-1 reverse transcriptase in the presence of magnesium.

Biochemistry. 42 (2003) 639-50.