ORBi: Close Pierre - DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation

Reference : DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elo...


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	To cite this reference:	http://hdl.handle.net/2268/116084

Title :	DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation
Language :	English
Author, co-author :	Close, Pierre [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
	East, Phil [ > > ]
	Svejstrup, Barbara [ > > ]
	Hartmann, Holger [ > > ]
	Heron, Mark [ > > ]
	Maslen, Sarah [ > > ]
	Chariot, Alain [Université de Liège - ULg > Département de pharmacie > Chimie médicale >]
	Söding, Johannes [ > > ]
	Skehel, Mark [ > > ]
	Svejstrup, Jesper [Cancer Research UK > Clare Hall Laboratories > Mechansims of Gene Transcription > >]
Publication date :	19-Apr-2012
Journal title :	Nature
Publisher :	Nature Publishing Group
Audience :	International
ISSN :	0028-0836
e-ISSN :	1476-4687
City :	Basingstoke
Country :	United Kingdom
Keywords :	[en] mRNP ; transcription ; RNA Polymerase II ; Alternative Splicing ; DBIRD
Abstract :	[en] Alternative messenger RNA splicing is the main reason that 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 elongation1–3. As the nascent pre-mRNA emerges from transcribing RNA polymerase II (RNAPII), it is assembled into a messenger ribonucleoprotein (mRNP) particle; this is the functional form of the nascent pre-mRNA and determines the fate of the mature transcript4. However, factors that connect the transcribing polymerase with the mRNP particle and help to integrate transcript elongation with mRNA splicing remain unclear. Here we characterize the human interactome of chromatin-associated mRNP particles. This led us to identify deleted in breast cancer 1 (DBC1) and ZNF326 (which we call ZNF-protein interacting with nuclear mRNPs and DBC1 (ZIRD)) as subunits of a novel protein complex—named DBIRD—that binds directly to RNAPII. DBIRD regulates alternative splicing of a large set of exons embedded in (A 1 T)-rich DNA, and is present at the affected exons. RNAinterference- mediated DBIRD depletion results in region-specific decreases in transcript elongation, particularly across areas encompassing affected exons. Together, these data indicate that the DBIRD complex acts at the interface between mRNP particles and RNAPII, integrating transcript elongation with the regulation of alternative splicing.
Research units :	Giga-Signal Transduction
Target :	Researchers
Permalink :	http://hdl.handle.net/2268/116084
DOI :	10.1038/nature10925
Other URL :	http://www.nature.com/nature/journal/vaop/ncurrent/full/nature10925.html
Commentary :	http://reflexions.ulg.ac.be/cms/c_43019/dbird-un-moteur-de-la-diversite-des-proteines

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