tailieunhanh - Báo cáo y học: "Murine leukemia virus RNA dimerization is coupled to transcription and splicing processes"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học 'Respiratory Research cung cấp cho các bạn kiến thức về ngành y đề tài: Murine leukemia virus RNA dimerization is coupled to transcription and splicing processes. | Maurel and Mougel Retrovirology 2010 7 64 http content 7 1 64 RETROVIROLOGY SHORT REPORT Open Access Murine leukemia virus RNA dimerization is coupled to transcription and splicing processes Stéphan Maurel Marylène Mougel Abstract Most of the cell biological aspects of retroviral genome dimerization remain unknown. Murine leukemia virus MLV constitutes a useful model to study when and where dimerization occurs within the cell. For instance MLV produces a subgenomic RNA called SD that is co-packaged with the genomic RNA predominantly as FLSD heterodimers. This SD RNA is generated by splicing of the genomic RNA and also by direct transcription of a splice-associated retroelement of MLV SDARE . We took advantage of these two SD origins to study the effects of transcription and splicing events on RNA dimerization. Using genetic approaches coupled to capture of RNA heterodimer in virions we determined heterodimerization frequencies in different cellular contexts. Several cell lines were stably established in which SD RNA was produced by either splicing or transcription from SDARE. Moreover SDARE was integrated into the host chromosome either concomitantly or sequentially with the genomic provirus. Our results showed that transcribed genomic and SD RNAs preferentially formed heterodimers when their respective proviruses were integrated together. In contrast heterodimerization was strongly affected when the two proviruses were integrated independently. Finally dimerization was enhanced when the transcription sites were expected to be physically close. For the first time we report that splicing and RNA dimerization appear to be coupled. Indeed when the RNAs underwent splicing the FLSD dimerization reached a frequency similar to co-transcriptional heterodimerization. Altogether our results indicate that randomness of heterodimerization increases when RNAs are co-expressed during either transcription or splicing. Our results strongly support the notion