Download or read book Up-frameshift Proteins and Their Distinct Roles in HIV-1 RNA Metabolism written by Lara Ajamian and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "HIV-1 co-opts host cell proteins at every step of its replication cycle to ensure proper replication. Our work identified that the HIV-1 genomic RNA is not a substrate for nonsense-mediated mRNA decay (NMD) even though it has multiple open reading frames as well as a long 3'UTR. We demonstrate that Up-frameshift protein 1 (UPF1) is involved in HIV-1 genomic RNA stability such that overexpression of UPF1 increases HIV-1 genomic RNA levels and Gag translation. Moreover, the role of UPF1 in HIV-1 is NMD-independent, is observed in both nuclear and cytoplasmic compartments and does not require binding to UPF2. Furthermore, the shuttling function of UPF1 is required for HIV-1 genomic RNA export since a UPF1 nuclear export mutant sequesters the genomic RNA in the nucleus and a nuclear localization mutant does not immunoprecipitate with the HIV-1 genomic RNA. UPF1's role in HIV-1 genomic RNA export is observed in both Rev-dependent and -independent conditions. In addition, UPF1 is found in complex with Rev, CRM1, Nup62 and DDX3, cellular proteins with already characterized roles in HIV-1 genomic RNA export. Lastly, we also identified UPF2 as a negative regulator, such that its binding to UPF1 results in the nuclear sequestration of the HIV-1 genomic RNA. We have identified a possible mechanism to explain how HIV-1 escapes the RNA quality control mechanism of NMD by co-opting UPF1 function for efficient HIV-1 genomic RNA export, stability and translation." --