2 resultados para regulation of transcription

em WestminsterResearch - UK


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Using the United Kingdom (UK) as a case study, this article analyses the growing commercial and regulatory significance of broadcaster-distributor relations within the contemporary television industry. The first part of the article argues that despite important changes in broadcast delivery technology, more recently shaped by the growth of the Internet, and the associated growth of options of receiving television content, the traditional delivery platforms (digital terrestrial, satellite and cable) remain by far the preferred choice for viewers in Britain. At the same time, public service broadcasters continue to be the biggest investors in domestic original non-sport content and account for over half of all television viewing. The strength of PSBs in content and their growing reliance on commercial proprietary subscription platforms (cable and satellite) and gradually on the Internet presents challenges in the nexus between broadcasters and distributors. The article focuses on the debate over retransmission fees between PSBs and Sky, and on the question of whether Sky should be required to offer some of its premium content to rival pay-TV platforms. These two examples highlight the impact regulatory intervention can have on the balance of power between broadcasters and distributors. The article concludes that such debates concerning the commercial relations between content providers and distributors will remain pivotal and become more heated given that similar issues are raised in the Internet environment.

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The human ZFP36 zinc finger protein family consists of ZFP36, ZFP36L1, and ZFP36L2. These proteins regulate various cellular processes, including cell apoptosis, by binding to adenine uridine rich elements in the 3′ untranslated regions of sets of target mRNAs to promote their degradation. The pro-apoptotic and other functions of ZFP36 family members have been implicated in the pathogenesis of lymphoid malignancies. To identify candidate mRNAs that are targeted in the pro-apoptotic response by ZFP36L1, we reverse-engineered a gene regulatory network for all three ZFP36 family members using the ‘maximum information coefficient’ (MIC) for target gene inference on a large microarray gene expression dataset representing cells of diverse histological origin. Of the three inferred ZFP36L1 mRNA targets that were identified, we focussed on experimental validation of mRNA for the pro-survival protein, BCL2, as a target for ZFP36L1. RNA electrophoretic mobility shift assay experiments revealed that ZFP36L1 interacted with the BCL2 adenine uridine rich element. In murine BCL1 leukemia cells stably transduced with a ZFP36L1 ShRNA lentiviral construct, BCL2 mRNA degradation was significantly delayed compared to control lentiviral expressing cells and ZFP36L1 knockdown in different cell types (BCL1, ACHN, Ramos), resulted in increased levels of BCL2 mRNA levels compared to control cells. 3′ untranslated region luciferase reporter assays in HEK293T cells showed that wild type but not zinc finger mutant ZFP36L1 protein was able to downregulate a BCL2 construct containing the BCL2 adenine uridine rich element and removal of the adenine uridine rich core from the BCL2 3′ untranslated region in the reporter construct significantly reduced the ability of ZFP36L1 to mediate this effect. Taken together, our data are consistent with ZFP36L1 interacting with and mediating degradation of BCL2 mRNA as an important target through which ZFP36L1 mediates its pro-apoptotic effects in malignant B-cells.