Etablishing links with pathology

To summarize: in the presence of DBIRD, the elongation speed of RNA polymerase II increases which causes the exclusion of exons rich in  A/T of the final messenger RNA.  On the other hand, in the absence of DBIRD, as the RNA polymerase II is slower, it has the time to transcribe the exons rich in A/T and these are therefore included in the mature messenger RNA. 

The discovery by the researchers of this new mechanism which regulates alternative splicing of mRNA by intermediary of transcription by RNA polymerase II was rewarded by being published in the journal Nature (1).

Another important aspect of this study is the presence of the DBC1 protein within the DBIRD complex. “This protein emanates from a gene which is in an impaired or absent locus in some breast cancers”, explains the scientist. “DBC1 plays a part in some other types of cancers such as cancer of the esophagus or prostate”, adds Pierre Close. “In addition to the discovery of a mechanism which links splicing to transcription, our study brings forth new information concerning the function of the DBC1 protein as well as the description of the ZIRD protein, which was unknown until now”,  he continues. The next step that Pierre Close and his colleagues at the Medical Chemistry Unit are going to take is to place these discoveries in a patho-physiological context.  Establishing links between DBIRD, and therefore DBC1and ZIRD, and possible pathologies, will make it possible to define whether this protein complex-or the proteins that it is composed of- could constitute an interesting target from a therapeutic point of view to fight these diseases.

(1). Pierre Close, Philip East, A. Barbara Dirac-Svejstrup, Holger Hartmann, Mark Heron, Sarah Maslen, Alain Chariot, Johannes Söding, Mark Skehel & Jesper Q. Svejstrup. DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation. Nature.