title: Additional 5' exons in the RGS3 locus generate multiple mRNA transcripts, one of which accounts for the origin of human PDZ-RGS3.
abstract: Regulators of G-protein signaling (RGS) proteins can be broadly divided into those that consist predominantly of an RGS domain and those that possess an RGS domain along with additional domains. RGS3 fits into both categories, as both short and longer forms exist. Recently, a novel form of mouse RGS3 that possesses a PDZ domain was identified. Here we show that the human PDZ-RGS3 isoform arises from 10 upstream exons along with 6 exons from the previously characterized RGS3. We found that 47,000 nucleotides span the last of the 10 upstream exons and the first exon used from the original cluster of RGS3 exons. These 10 upstream exons encode 398 amino acids, which show strong conservation with those from mouse PDZ-RGS3. In addition, another isoform exists that uses 17 upstream exons, 9 of which overlap with those in PDZ-RGS3, along with the same 6 downstream exons used in PDZ-RGS3. Finally, a short form of human RGS3 arises from an unrecognized RGS3 exon that encodes an amino-terminal 140 amino acids. For each RGS3 isoform, RT-PCR detected specific mRNA transcripts and immunoblot analysis identified specific bands for RGS3 and PDZ-RGS3. RGS3 provides an example of the complex origins of the coding regions of mammalian proteins.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. jkehrl@niaid.nih.gov
authors.forename: John H
authors.initials: JH
authors.lastname: Kehrl
authors.forename: Deepa
authors.initials: D
authors.lastname: Srikumar
authors.forename: Kathleen
authors.initials: K
authors.lastname: Harrison
authors.forename: Gaye L
authors.initials: GL
authors.lastname: Wilson
authors.forename: Chong-Shan
authors.initials: CS
authors.lastname: Shi
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics*; D019143:Evolution, Molecular; D005091:Exons; D019204:GTP-Binding Proteins / Q000235:genetics; D020690:GTPase-Activating Proteins; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D020033:Protein Isoforms; D020710:RGS Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020539:Sequence Analysis, Protein
chemical_list: D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D020033:Protein Isoforms; D020710:RGS Proteins; C485898:RGS3 protein, human; C415085:Rgs3 protein, mouse; D019204:GTP-Binding Proteins