The C-terminal domain of SRA1p has a fold more similar to PRP18 than to an RRM and does not directly bind to the SRA1 RNA STR7 region.
Steroid receptor activator RNA protein (SRA1p) is the translation product of the bi-functional long non-coding RNA steroid receptor activator RNA 1 (SRA1) that is part of the steroid receptor coactivator-1 acetyltransferase complex and is indicated to be an epigenetic regulatory component. Previously, the SRA1p protein was suggested to contain an RNA recognition motif (RRM) domain. We have determined the solution structure of the C-terminal domain of human SRA1p by NMR spectroscopy. Our structure along with sequence comparisons among SRA1p orthologs and against authentic RRM proteins indicates that it is not an RRM domain but rather an all-helical protein with a fold more similar to the PRP18 splicing factor. NMR spectroscopy on the full SRA1p protein suggests that this structure is relevant to the native full-length context. Furthermore, molecular modeling indicates that this fold is well conserved among vertebrates. Amino acid variations in this protein seen across sequenced human genomes, including those in tumor cells, indicate that mutations that disrupt the fold occur vary rarely and highlight that its function is well conserved. SRA1p had previously been suggested to bind to the SRA1 RNA, but NMR spectra of SRA1p in the presence of its 80-nt RNA target suggest otherwise and indicate that this protein must be part of a multi-protein complex in order to recognize its proposed RNA recognition element.
Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA.
Stephanie M
SM
Bilinovich
Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA.
Caroline M
CM
Davis
Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA.
Daniel L
DL
Morris
Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA.
Louis A
LA
Ray
Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, USA.
Jeremy W
JW
Prokop
Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA.
Gregory J
GJ
Buchan
Department of Chemistry and Biochemistry, The University of Akron, Akron, OH 44325, USA. Electronic address: tleeper@uakron.edu.
Thomas C
TC
Leeper
D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D062085:RNA, Long Noncoding / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017415:Ribonucleoprotein, U5 Small Nuclear / Q000737:chemistry* / Q000235:genetics; D012261:Ribonucleoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
D002352:Carrier Proteins; C080779:PRP18 protein, S cerevisiae; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D011994:Recombinant Proteins; D017415:Ribonucleoprotein, U5 Small Nuclear; D012261:Ribonucleoproteins; D029701:Saccharomyces cerevisiae Proteins; C548898:steroid receptor RNA activator, human
NMR; SRA1p; epigenetics; lncRNA; steroid receptor activator RNA