Elsevier

Genomics

Volume 79, Issue 6, June 2002, Pages 860-868
Genomics

Regular Article
Additional 5′ Exons in the RGS3 Locus Generate Multiple mRNA Transcripts, One of Which Accounts for the Origin of Human PDZ-RGS3

https://doi.org/10.1006/geno.2002.6773Get rights and content

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.

Cited by (32)

  • Emerging Roles of Regulators of G Protein Signaling (RGS) Proteins in the Immune System

    2017, Advances in Immunology
    Citation Excerpt :

    Further mechanistic studies of T cell migration patterns at baseline and during inflammatory pathology will need to be done to determine the functions of RGS2 in adaptive immune responses. Unlike other members of the R4 subfamily that consist of little more than the RGS domain, RGS3 has several splice variants including a larger protein containing a PDZ motif, which has been shown to bind B-ephrin receptors to modulate their signaling (Kehrl, Srikumar, Harrison, Wilson, & Shi, 2002; Lu, Sun, Klein, & Flanagan, 2001). RGS3 was upregulated in splenic Th1 and Th2 cells differentiated from naïve splenocytes in vitro, and RGS3 KD augmented chemotaxis of T cell lines (EL4) to CXCL12 and CCL19 (Williams et al., 2013).

  • The impact of RGS and other G-protein regulatory proteins on Gα<inf>i</inf>-mediated signaling in immunity

    2016, Biochemical Pharmacology
    Citation Excerpt :

    There are several RGS3 splice variants that encode for proteins with additional domains. One variant termed PDZ-RGS3 has N terminal PDZ domain, which can bind type B ephrins, an ATP/GTP-binding site, and a proline-rich region of unknown function [97,98]. A loss of PDZ-RGS3 in mice caused an early cell cycle exit and precocious differentiation of neural progenitor cells located in the developing cerebral cortex, a phenotype similar to that observed in the ephrin-B1 knockout mice.

  • Regulators of G-Protein-Signaling Proteins: Negative Modulators of G-Protein-Coupled Receptor Signaling

    2015, International Review of Cell and Molecular Biology
    Citation Excerpt :

    RGS3 has several spliced variant forms that all come from the RGS3 gene. A short form, RGS3S, which contains little more than the RGS domain, was expressed in the nucleus and induced apoptosis when overexpressed (Dulin et al., 2000; Jaen and Doupnik, 2005; Kehrl et al., 2002; Tosetti and Dunlap, 2004). RGS3 has two longer isoforms, RGS3L and PDZ-RGS3 (Kehrl et al., 2002), the latter of which has been linked to cell migration through interaction with Ephrin receptors and in Gβγ-evoked signaling.

  • Regulator of G-protein signaling 3 isoform 1 (PDZ-RGS3) enhances canonical Wnt signaling and promotes epithelial mesenchymal transition

    2012, Journal of Biological Chemistry
    Citation Excerpt :

    Whereas full-length PDZ-RGS3 increased the levels of cytosolic β-catenin and c-myc, the RGS domain or PDZ domain-deleted versions had much less effect (Fig. 2A). We also compared PDZ-RGS3 with RGS3L, which contains the C-terminal 519 amino acids of PDZ-RGS3 (16). Expression of PDZ-RGS3 increased cyclin D1, another Wnt target gene (23), and c-myc whereas RGS3L expression had only a modest effect despite its much higher expression (Fig. 2B).

  • Regulators of G protein signaling proteins as targets for drug discovery

    2010, Progress in Molecular Biology and Translational Science
  • Chapter 2 Insights into RGS Protein Function from Studies in Caenorhabditis elegans

    2009, Progress in Molecular Biology and Translational Science
    Citation Excerpt :

    Proteins of the B/R4 family, often considered a mammal‐specific family, in general have no features outside the RGS domain. The one exception is human RGS‐3, which has an alternative isoform known as C2PA‐RGS‐3, that also contains a C2 domain.15 C. elegans RGS‐7 also has a C2 domain16 and we have therefore assigned it to the B/R4 family.

View all citing articles on Scopus
*

To whom correspondence and reprint requests should be addressed. Fax: (301) 402-0070. E-mail: [email protected].

View full text