HeLa37 cells were treated with the indicated amounts of DRB for 1 hour and lyse

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 HeLa37 cells were treated with the indicated amounts of DRB for 1 hour and lyse Empty HeLa37 cells were treated with the indicated amounts of DRB for 1 hour and lyse

Post  huwan123456 on Wed May 14, 2014 6:03 am

However, the targeting sites of miRNA or siRNA on gene promoter in previous studies distribute in a wide range. In this study, miR H3 targets the key [You must be registered and logged in to see this link.] position for transcription initiation TATA box, wherein the poly merase II pre initiation complexes are assembled. This finding raises the possibility that miRNAs directly participate in the transcription initiation regulation in mammalian cells. The transcription activity of HIV 1 provirus is finely modulated in different host cells, which is accomplished through a lot of cellular transcription factors and viral proteins. Cellular transcription factors such as Sp1, NF κB, NF AT, LEF 1 TCF 1, C EBP, and CREB are important for the activation of HIV 1 LTR driven tran scription, Conversely, cellular factors including LBP 1, TDP 43, YY1 and P53 exhibit inhibitory effects on LTR driven transcription.

It is noteworthy that the effects of many cellular factors are cell type dependent and there are complicated interaction among these factors. A key viral regulator of HIV 1 transcription activity is the regulatory protein Tat, which is produced during early phase of infection [You must be registered and logged in to see this link.] and binds to the trans activation responsive region located at the 5 end of viral mRNAs. After binding, Tat recruits a diverse series of transcriptional complexes to the viral promoter and activates transcription activity. These com plexes include enzymes with histone and factor acetyl transferase activities, which modify chromatin conformation at the proviral integration site, and a protein complex that hyper phosphorylates the carboxy terminal domain of RNA polymerase II, thus promoting the initiation and elongation of viral transcription.

Vpr and Nef also have effects on HIV 1 transcription, which through the interaction with Tat or up regulating the expression of ac tivating factors such as NF AT, NF κB, and AP 1. [You must be registered and logged in to see this link.] In this study, we showed that miR H3 is another HIV 1 encoded cis regulatory element, in addition to Tat, that direct interacts with viral element and regulates transcrip tion activity. It is interesting to investigate whether the ef fect of miR H3 is cell type dependent and identify its cellular co factors. Our findings further reveal the com plexity of transcription regulation for HIV 1. The advances in next generation sequencing technol ogy have greatly fueled the discovery of small RNAs, especially the low expressed miRNAs.

However, their functions are largely unexploited. One opinion about these low expressed miRNAs is that they may not have function due to the low expression levels. This idea is reasonable according to the well known paradigm that miRNAs function in cytoplasm through targeting the 3 UTR of mRNA for translation repression. This model requires a considerable amount of miRNAs for their func tions since their targets are relatively highly expressed. But our data suggest miR H3 and many cellular miRNAs tar get the core promoter of HIV 1 virus and many important genes, which are on the chromosomal DNA with very limited copy number in the nucleus in contrast to the massive mRNA molecules in the cyto plasm. Thus the requirement of the accumulation level of these TATA box targeting miRNAs is relatively low.

huwan123456

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