1,721,059 research outputs found
Integrator complex and transcription regulation: Recent findings and pathophysiology
No full textIn the last decade, a novel molecular complex has been added to the RNA polymerase II-mediated transcription machinery as one of the major components. This multiprotein complex, named Integrator, plays a pivotal role in the regulation of most RNA Polymerase II-dependent genes. This complex consists of at least 14 different subunits. However, studies investigating its structure and composition are still lacking. Although it was originally discovered as a complex implicated in the 3'-end formation of noncoding small nuclear RNAs, recent studies indicate additional roles for Integrator in transcription regulation, for example during transcription pause release and elongation of polymerase, in the biogenesis of transcripts derived from enhancers, as well as in DNA and RNA metabolism for some of its components. Noteworthy, several subunits have been emerging to play roles during development and differentiation; more importantly, their alterations are likely to be involved in several human pathologies, including cancer and lung diseases. (C) 2016 Elsevier B.V. All rights reserved
Gene expression profile of the whole Mediator complex in human osteosarcoma and normal osteoblasts
No full textMediator complex (MED) is an essential multi-subunit component of the transcription apparatus and plays a key role in the transcription regulation of many genes involved in several diseases, including cancer. Recently, numerous MED subunits have been implicated in cancer development and metastasis, and specific alterations in their coding genes have been found to correlate with some malignancies. It is conceivable that a specific MED alteration pattern can characterize each cancer type. However, to date, no study has reported the complete picture of MED subunits in a specific tumor. Thus, the aim of this study was to investigate for the first time the gene expression profile of the whole MED complex in human osteosarcoma (OS). To this purpose, we have examined all the MED subunit genes in three OS cell lines compared to normal osteoblasts by real-time RT-PCR. Interestingly, our findings indicate that the expression of most of the MED genes is altered in OS. Moreover, a very high overexpression of MED20 and MED31 can be observed in all the analyzed OS cells, thus suggesting for the first time a potential role of these subunits in human malignancies. Overall, this study may open the way to other functional studies exploring the role of the whole complex in cancer development and progression. These findings may lead to the identification of novel biomarkers, which can be used also in combination with imaging techniques for early detection, and/or to develop novel targets for innovative therapeutic approaches. © 2013 Springer Science+Business Media New York
Kidney and heart interactions during cardiorenal syndrome: a molecular and clinical pathogenic framework
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