Reactome | RNase H-mediated cleavage of the RNA strand of the -sssDNA:RNA duplex

RNase H-mediated cleavage of the RNA strand of the -sssDNA:RNA duplex

Stable Identifier

R-HSA-164519

Type

Reaction [transition]

Species

Homo sapiens

Related Species

Human immunodeficiency virus 1

Compartment

cytosol

ReviewStatus

5/5

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Disease (Homo sapiens)

- Infectious disease (Homo sapiens)
  - Viral Infection Pathways (Homo sapiens)
    - HIV Infection (Homo sapiens)
      - HIV Life Cycle (Homo sapiens)
        
        Early Phase of HIV Life Cycle (Homo sapiens)
        
        Reverse Transcription of HIV RNA (Homo sapiens)
        
        Minus-strand DNA synthesis (Homo sapiens)
        
        RNase H-mediated cleavage of the RNA strand of the -sssDNA:RNA duplex (Homo sapiens)

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RNase H-mediated cleavage of the RNA strand of the -sssDNA:RNA duplex

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As the reverse transcriptase activity of the HIV-1 RT heterodimer catalyzes the synthesis of minus-strand strong stop DNA (-sssDNA), the RNaseH activity of the same RT heterodimer catalyzes the degradation of the complementary viral genomic RNA sequences. Degradation of this RNA is required for the efficient transfer of the -sssDNA to the 5' end of the viral genomic RNA. The RNase H active site is positioned within the HIV-1 RT heterodimer so as to attack the RNA strand of the RNA:DNA duplex at a point 18 bases behind the site of reverse transcription (Furfine and Reardon 1991; Ghosh et al. 1995; Gopalakrishnan et al. 1992; Wohrl and Moelling 1990). The rate of RNase H cleavage is substantially lower than the rate of DNA synthesis, however (Kati et al. 1992), and may further depend on RT stalling and structural features of the viral genomic RNA template. The product of these combined DNA synthesis and RNA degradation events is a DNA strand still duplexed with extended viral genomic RNA fragments.

Literature References

PubMed ID	Title	Journal	Year
7535765	Truncating alpha-helix E' of p66 human immunodeficiency virus reverse transcriptase modulates RNase H function and impairs DNA strand transfer Ghosh, M, Howard, KJ, Cameron, CE, Benkovic, SJ, Hughes, SH, Le Grice, SF	J Biol Chem	1995
10723025	The HIV-1 reverse transcription (RT) process as target for RT inhibitors Jonckheere, H, Anne, J, De Clercq, E	Med Res Rev	2000
1702425	Reverse transcriptase.RNase H from the human immunodeficiency virus. Relationship of the DNA polymerase and RNA hydrolysis activities. Furfine, ES, Reardon, JE	J Biol Chem	1991
	Retroviruses Coffin, JM, Hughes, SH, Varmus, HE		1997