Loading...
Please wait, while we are loading the content...
Similar Documents
DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation.
| Content Provider | Europe PMC |
|---|---|
| Author | Close, Pierre East, Philip Dirac-Svejstrup, A. Barbara Hartmann, Holger Heron, Mark Maslen, Sarah Chariot, Alain Söding, Johannes Skehel, Mark Svejstrup, Jesper Q. |
| Abstract | Alternative mRNA splicing is the main reason vast mammalian proteomic complexity can be achieved with a limited number of genes. Splicing is physically and functionally coupled to transcription, and is greatly affected by the rate of transcript elongation1,2,3. As the nascent pre-mRNA emerges from transcribing RNA polymerase II (RNAPII), it is assembled into a messenger ribonucleoprotein (mRNP) particle which is its functional form and determines the fate of the mature transcript4. However, factors that connect the transcribing polymerase with the mRNP particle and help integrate transcript elongation with mRNA splicing remain obscure. Here, we characterized the interactome of chromatin-associated mRNP particles. This led to the identification of Deleted in Breast Cancer 1 (DBC1) and a protein we named ZIRD as subunits of a novel protein complex, named DBIRD, which binds directly to RNAPII. DBIRD regulates alternative splicing of a large set of exons embedded in A/T-rich DNA, and is present at the affected exons. RNAi-mediated DBIRD depletion results in region-specific decreases in transcript elongation, particularly across areas encompassing affected exons. Together, these data indicate that DBIRD complex acts at the interface between mRNP particles and RNAPII, integrating transcript elongation with the regulation of alternative splicing. |
| ISSN | 00280836 |
| Volume Number | 484 |
| PubMed Central reference number | PMC3378035 |
| Issue Number | 7394 |
| PubMed reference number | 22446626 |
| Journal | Nature |
| e-ISSN | 14764687 |
| DOI | 10.1038/nature10925 |
| Language | English |
| Publisher Date | 2012-03-25 |
| Access Restriction | Open |
| Rights License | Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
