Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) is a host cytidine deaminase that is packaged into virions and confers resistance to retroviral infection. APOBEC3G deaminates deoxycytidines in minus strand DNA to deoxyuridines, resulting in G to A hypermutation and viral inactivation. Human immunodeficiency virus type 1 (HIV-1) virion infectivity factor counteracts the antiviral activity of APOBEC3G by inducing its proteosomal degradation and preventing virion incorporation. To elucidate the mechanism of viral suppression by APOBEC3G, we developed a sensitive cytidine deamination assay and analyzed APOBEC3G virion incorporation in a series of HIV-1 deletion mutants. Virus-like particles derived from constructs in which pol, env, and most of gag were deleted still contained high levels of cytidine deaminase activity; in addition, coimmunoprecipitation of APOBEC3G and HIV-1 Gag in the presence and absence of RNase A indicated that the two proteins do not interact directly but form an RNase-sensitive complex. Viral particles lacking HIV-1 genomic RNA which were generated from the gag-pol expression constructs pC-Help and pSYNGP packaged APOBEC3G at 30-40% of the wild-type level, indicating that interactions with viral RNA are not necessary for incorporation. In addition, viral particles produced from an nucleocapsid zinc finger mutant contained approximately 1% of the viral genomic RNA but approximately 30% of the cytidine deaminase activity. The reduction in APOBEC3G incorporation was equivalent to the reduction in the total RNA present in the nucleocapsid mutant virions. These results indicate that interactions with viral proteins or viral genomic RNA are not essential for APOBEC3G incorporation and suggest that APOBEC3G interactions with viral and nonviral RNAs that are packaged into viral particles are sufficient for APOBEC3G virion incorporation.
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PMID:Human apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) is incorporated into HIV-1 virions through interactions with viral and nonviral RNAs. 1521 Jul 4

An insertion of 6.4 kb is present in intron 9 of 60% of the human complement C4 genes, as well as in the C4 genes of a number of Old World primates. This insertion has the typical genomic organization of endogenous retroviruses, with the three major genes gag, pol and env flanked by long terminal repeats (LTRs). This human endogenous retrovirus K [HERV-K(C4)] insertion is in reverse orientation to the C4 coding sequence. Using RT-PCR as well as RNase protection assays, retroviral transcripts could be detected in different human cell lines which were only present in the antisense orientation of the retrovirus. Furthermore, C4 expression as well as intermediate transcripts comprising both HERV-K(C4) and C4 coding sequences was observed in these cells. These findings were confirmed using real-time PCR to quantitate the number of specific mRNA transcripts. Using reporter gene assays, it could be demonstrated that only the 3'LTR exhibits promoter activity, but in the sense orientation of the retrovirus. It has been suggested earlier that expression of C4 could lead to the transcription of a retroviral antisense RNA, which might protect against exogenous retroviral infections. In a previous study, it was shown that the expression of retroviral-like constructs was significantly downregulated in mouse cells transfected with human C4 genes, and that this downregulation was further modulated after IFN-gamma stimulation of C4 expression. In a new series of experiments, we have now confirmed these observations, using human hepatoma cells constitutively expressing C4. A dose-dependent downregulation of up to 45% caused by hybridization of retroviral sense and genomic HERV-K(C4) antisense RNA was observed. The functional 3'LTR promoter, the presence of retroviral antisense RNA transcripts and the functional detection of HERV-K(C4)-specific antisense activity provide strong evidence for a major role of the HERV-K(C4) insertion in the control of gene expression, resulting in a selective advantage favouring the presence of this element in human and primate C4 genes.
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PMID:Detection of retroviral antisense transcripts and promoter activity of the HERV-K(C4) insertion in the MHC class III region. 1530 46


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