A steroid receptor coactivator, SRA, functions as an RNA and is present in an SRC-1 complex.
Nuclear receptors play critical roles in the regulation of eukaryotic gene expression. We report the isolation and functional characterization of a novel transcriptional coactivator, termed steroid receptor RNA activator (SRA). SRA is selective for steroid hormone receptors and mediates transactivation via their amino-terminal activation function. We provide functional and mechanistic evidence that SRA acts as an RNA transcript; transfected SRA, unlike other steroid receptor coregulators, functions in the presence of cycloheximide, and SRA mutants containing multiple translational stop signals retain their ability to activate steroid receptor-dependent gene expression. Biochemical fractionation shows that SRA exists in distinct ribonucleoprotein complexes, one of which contains the nuclear receptor coactivator steroid receptor coactivator 1. We suggest that SRA may act to confer functional specificity upon multiprotein complexes recruited by liganded receptors during transcriptional activation.
Lanz
R B
RB
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
McKenna
N J
NJ
Onate
S A
SA
Albrecht
U
U
Wong
J
J
Tsai
S Y
SY
Tsai
M J
MJ
O'Malley
B W
BW
D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000302:isolation & purification; D051548:Histone Acetyltransferases; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D056920:Nuclear Receptor Coactivator 1; D012313:RNA / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D011987:Receptors, Steroid / Q000235:genetics / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*
D018076:DNA, Complementary; D046911:Macromolecular Substances; D046912:Multiprotein Complexes; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D015534:Trans-Activators; D014157:Transcription Factors; D012313:RNA; D051548:Histone Acetyltransferases; C538859:NCOA1 protein, human; C538861:Ncoa1 protein, mouse; D056920:Nuclear Receptor Coactivator 1