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Bipartite functions of the CREB co‐activators selectively direct alternative splicing or transcriptional activation
Author(s) -
Amelio Antonio L,
Caputi Massimo,
Conkright Michael D
Publication year - 2009
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2009.216
Subject(s) - biology , alternative splicing , creb , computational biology , genetics , microbiology and biotechnology , transcription factor , gene , exon
The CREB regulated transcription co‐activators (CRTCs) regulate many biological processes by integrating and converting environmental inputs into transcriptional responses. Although the mechanisms by which CRTCs sense cellular signals are characterized, little is known regarding how CRTCs contribute to the regulation of cAMP inducible genes. Here we show that these dynamic regulators, unlike other co‐activators, independently direct either pre‐mRNA splice‐site selection or transcriptional activation depending on the cell type or promoter context. Moreover, in other scenarios, the CRTC co‐activators coordinately regulate transcription and splicing. Mutational analyses showed that CRTCs possess distinct functional domains responsible for regulating either pre‐mRNA splicing or transcriptional activation. Interestingly, the CRTC1–MAML2 oncoprotein lacks the splicing domain and is incapable of altering splice‐site selection despite robustly activating transcription. The differential usage of these distinct domains allows CRTCs to selectively mediate multiple facets of gene regulation, indicating that co‐activators are not solely restricted to coordinating alternative splicing with increase in transcriptional activity.