Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two types of serotonin 2C subtype receptor mRNA, receptor-type and short variant, has been reported. The expression of the receptor-type mRNA could be detected as well as the short variant in NG108-15 cells by using a high temperature stable reverse transcriptase and the expression of the receptor-type mRNA was enhanced in drug-induced neuronal differentiated cells. The deleted sequence of the short variant include the RNA editing site by adenosine deaminase. Analysis of the sequence at the editing site revealed that the mRNA of undifferentiated cells was highly edited at sites A and B and that cytosine deaminase activity may also be involved in neuronal differentiation.
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PMID:RNA editing and short variant of serotonin 2C receptor mRNA in neuronally differentiated NG108-15 cells. 1549 66

Human immune cells infected by HIV naturally contain high uracil content, and HIV reverse transcriptase (RT) does not distinguish between dUTP and dTTP. Many DNA viruses and retroviruses encode a dUTPase or uracil-DNA glycosylase (UNG) to counteract uracil incorporation. However, although HIV virions are thought to contain cellular UNG2, replication of HIV produced in cells lacking UNG activity does not appear to be impaired. Here we show that HIV reverse transcripts generated in primary human immune cells are heavily uracilated (>500 uracils per 10 kb HIV genome). We find that HIV DNA uracilation, rather than being dangerous, may promote the early phase of the viral life cycle. Shortly after reverse transcription, the ends of the HIV DNA are activated by the viral integrase (IN) in preparation for chromosomal insertion. However, the activated ends can attack the viral DNA itself in a suicidal side pathway, called autointegration. We find here that uracilation of target DNA inhibits the strand transfer of HIV DNA ends by IN, thereby inhibiting autointegration and facilitating chromosomal integration and viral replication. When uracilation is increased by incubating uracil-poor cells in the presence of increasing concentrations of dUTP or by infecting with virus that contains the cytosine deaminase APOBEC3G (A3G), the proportion of reverse transcripts that undergo suicidal autointegration decreases. Thus, HIV tolerates, or even benefits from, nonmutagenic uracil incorporation during reverse transcription in human immune cells.
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PMID:HIV DNA is heavily uracilated, which protects it from autointegration. 2157 78

It is well established that the cytosine deaminase APOBEC3G can restrict HIV-1 virions in the absence of the virion infectivity factor (Vif) by inducing genome mutagenesis through deamination of cytosine to uracil in single-stranded HIV-1 (-)DNA. However, whether APOBEC3G is able to restrict HIV-1 using a deamination-independent mode remains an open question. In this report we use in vitro primer extension assays on primer/templates that model (-)DNA synthesis by reverse transcriptase from the primer binding site (PBS) and within the protease gene of HIV-1. We find that APOBEC3G is able to decrease the initiation of DNA synthesis by reverse transcriptase approximately 2-fold under conditions where reverse transcriptase is in excess to APOBEC3G, as found in HIV-1 virions. However, the delay in the initiation of DNA synthesis on RNA templates up to 120 nt did not decrease the total amount of primer extended after extended incubation unless the concentration of reverse transcriptase was equal to or less than that of APOBEC3G. By determining apparent Kd values of reverse transcriptase and APOBEC3G for the primer/templates and of reverse transcriptase binding to APOBEC3G we conclude that APOBEC3G is able to decrease the efficiency of reverse transcriptase-mediated DNA synthesis by binding to the RNA template, rather than by physically interacting with reverse transcriptase. All together the data support a model in which this deamination-independent mode of APOBEC3G would play a minor role in restricting HIV-1. We propose that the deamination-independent inhibition of reverse transcriptase we observed can be a mechanism used by APOBEC3G to slow down proviral DNA formation and increase the time in which single-stranded (-)DNA is available for deamination by APOBEC3G, rather than a direct mechanism used by APOBEC3G for HIV-1 restriction.
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PMID:Retroviral restriction factor APOBEC3G delays the initiation of DNA synthesis by HIV-1 reverse transcriptase. 2371 65

The APOBEC3 family of cytosine deaminase enzymes are able to restrict replication of retroelements, such as LINE-1. However, each of the seven APOBEC3 enzymes have been reported to act differentially to prevent LINE-1 retrotransposition and the mechanisms of APOBEC3-mediated LINE-1 inhibition has not been well understood. The prevailing view for many years was that APOBEC3-mediated LINE-1 inhibition was deamination-independent and relied on APOBEC3s blocking the LINE-1 reverse transcriptase DNA polymerization or transport of the LINE-1 RNA into the nucleus. However, recently it was shown that APOBEC3A can deaminate cytosine, to form uracil, on transiently exposed single-stranded LINE-1 cDNA and this leads to LINE-1 cDNA degradation. In this study, we confirmed that APOBEC3A is a potent deamination-dependent inhibitor of LINE-1 retrotransposition, but show that in contrast, A3H haplotype II and haplotype V restrict LINE-1 activity using a deamination-independent mechanism. Our study supports the model that different APOBEC3 proteins have evolved to inhibit LINE-1 retrotransposition through distinct mechanisms.
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PMID:Deamination-independent restriction of LINE-1 retrotransposition by APOBEC3H. 2888 57