Steroid hormone receptor coactivation and alternative RNA splicing by U2AF65-related proteins CAPERalpha and CAPERbeta.
Increasing evidence indicates that transcription and pre-mRNA processing are functionally coupled to modulate gene expression. Here, we report that two members of the U2AF65 family of proteins, hCC1.3, which we call CAPERalpha, and a related protein, CAPERbeta, regulate both steroid hormone receptor-mediated transcription and alternative splicing. The CAPER proteins coactivate the progesterone receptor in luciferase transcription reporter assays and alter alternative splicing of a calcitonin/calcitonin gene-related peptide minigene in a hormone-dependent manner. The importance of CAPER coactivators in the regulation of alternative RNA splicing of an endogenous cellular gene (VEGF) was substantiated by siRNA knockdown of CAPERalpha. Mutational analysis of CAPERbeta indicates that the transcriptional and splicing functions are located in distinct and separable domains of the protein. These results indicate that steroid hormone receptor-regulated transcription and pre-mRNA splicing can be directly linked through dual function coactivator molecules such as CAPERalpha and CAPERbeta.
Dowhan
Dennis H
DH
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Hong
Eugene P
EP
Auboeuf
Didier
D
Dennis
Andrew P
AP
Wilson
Michelle M
MM
Berget
Susan M
SM
O'Malley
Bert W
BW
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002522:Chlorocebus aethiops; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D011987:Receptors, Steroid / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012261:Ribonucleoproteins / Q000235:genetics* / Q000378:metabolism*; D000072668:Splicing Factor U2AF; D015533:Transcriptional Activation; D014162:Transfection
D047628:Estrogen Receptor alpha; D009687:Nuclear Proteins; D012322:RNA Precursors; D034741:RNA, Small Interfering; D011980:Receptors, Progesterone; D011987:Receptors, Steroid; D011993:Recombinant Fusion Proteins; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C000607494:U2AF2 protein, human; D015740:Calcitonin Gene-Related Peptide