SIPP1, a novel pre-mRNA splicing factor and interactor of protein phosphatase-1

Llorian, Miriam; Beullens, Monique; Andrés, Isabel; Ortiz, JoséM.; Bollen, Mathieu

doi:10.1042/bj20030950

Cited by 52 publications

(46 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Endogenous FBP21 colocalizes with the essential splicing factor SC35 in the nuclear speckles (6), which contain numerous pre-mRNA splicing factors (10,35,36). EGFP-tagged FBP21 also partially colocalized with SC35 in the nuclear speckles in both HEK293T cells (Fig.…”

Section: Ww Domains Mediate the Interaction Of Fbp21 Withmentioning

confidence: 99%

“…The sequences of the DNA constructs were verified by DNA sequencing. The constructs GST-SIPP1-(1-372), GST-SIPP1-(180 -372), GST-SIPP1-(253-641), and GST-SIPP1-(358 -641) were obtained as described (10). 15 N-labeled mutant proteins were produced in the same way.…”

Section: Methodsmentioning

confidence: 99%

“…Antibodies-Polyclonal antibodies against SIPP1 were raised in rabbits, as described previously (10). Anti-EGFP and antirabbit secondary antibodies were purchased from Santa Cruz Biotechnology (Santa Cruz, CA) and Dako (Denmark), respectively.…”

Section: Methodsmentioning

confidence: 99%

“…1) that are capable of binding to the WW domain of PQBP1 (polyglutamine tract-binding protein 1) and functions as a pre-mRNA splicing activator in intact cells (10). SIPP1 is also present in the sub-spliceosomal complex containing FBP21, suggesting that it is also a candidate interactor of FBP21.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Structure and Function of the Two Tandem WW Domains of the Pre-mRNA Splicing Factor FBP21 (Formin-binding Protein 21)

Huang

Beullens

Zhang

et al. 2009

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Human FBP21 (formin-binding protein 21) contains a matrin-type zinc finger and two tandem WW domains. It is a component of the spliceosomes and interacts with several established splicing factors. Here we demonstrate for the first time that FBP21 is an activator of pre-mRNA splicing in vivo and that its splicing activation function and interaction with the splicing factor SIPP1 (splicing factor that interacts with PQBP1 and PP1) are both mediated by the two tandem WW domains of group III. We determined the solution structure of the tandem WW domains of FBP21 and found that the WW domains recognize peptide ligands containing either group II (PPLP) or group III (PPR) motifs. The binding interfaces involve both the XP and XP2 grooves of the two WW domains. Significantly, the tandem WW domains of FBP21 are connected by a highly flexible region, enabling their simultaneous interaction with two proline-rich motifs of SIPP1. The strong interaction between SIPP1 and FBP21 can be explained by the conjugation of two low affinity interactions with the tandem WW domains. Our study provides a structural basis for understanding the molecular mechanism underlying the functional implication of FBP21 and the biological specificity of tandem WW domains.Gene expression in eukaryotic cells involves several steps, including transcription, mRNA processing, and export. Pre-mRNA splicing takes place in the spliceosome, a highly dynamic ribonucleoprotein particle that consists of five small nuclear RNAs and at least 150 proteins. Small nuclear ribonucleoproteins (snRNPs) 3 and numerous protein factors are essential for the formation of the active spliceosome (1, 2). In budding yeast, the splicing factor Prp40 participates in crossintron bridging by interacting with the branch point-binding protein (BBP) and the U5 snRNP component Prp8. Prp40 contacts the 5Ј splice site and interacts with BBP, bringing the 5Ј splice site and the branch point in spatial proximity. These interactions are believed to be conserved in mammals (3-5). FBP21 (formin-binding protein 21), the mammalian Prp40-like protein, colocalizes with splicing factors in nuclear storage sites for pre-mRNA splicing factors. In addition, FBP21 is a component of the mammalian spliceosomal A/B complex and is associated with U2 snRNPs (6). FBP21 interacts directly with the splicing factors U1 snRNP protein U1C, the core snRNP proteins SmB and SmBЈ, and the branch point-binding protein SF1/mBBP, suggesting that it may also play a role in crossintron bridging of U1 and U2 snRNPs in the spliceosomes. FBP21 contains a matrin-type zinc finger and two group III WW domains ( Fig. 1) that are structurally related to those of the established splicing factors U1C and Prp40, respectively (6, 7). The binding of FBP21 to splicing factors is mediated by its tandem WW domains, which represent interaction modules for proline-rich ligands (4, 8, 9). Although the above data strongly suggest that FBP21 has a role in pre-mRNA splicing, there are no in vivo data to support this contention. The splicing...

show abstract

Section: Ww Domains Mediate the Interaction Of Fbp21 Withmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Structure and Function of the Two Tandem WW Domains of the Pre-mRNA Splicing Factor FBP21 (Formin-binding Protein 21)

Huang

Beullens

Zhang

et al. 2009

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…PCR site-directed mutagenesis was used to create the HA-PQBP1-Y65C mutant. The source of rabbit polyclonal antibodies against WBP11 and PQBP1 was previously described (7,22). Anti-hemagglutinin antibodies were purchased from Santa Cruz Biotechnology.…”

Section: Methodsmentioning

confidence: 99%

Y65C Missense Mutation in the WW Domain of the Golabi-Ito-Hall Syndrome Protein PQBP1 Affects Its Binding Activity and Deregulates Pre-mRNA Splicing

Tapia

Nicolaescu

McDonald

et al. 2010

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The PQBP1 (polyglutamine tract-binding protein 1) gene encodes a nuclear protein that regulates pre-mRNA splicing and transcription. Mutations in the PQBP1 gene were reported in several X chromosome-linked mental retardation disorders including Golabi-Ito-Hall syndrome. The missense mutation that causes this syndrome is unique among other PQBP1 mutations reported to date because it maps within a functional domain of PQBP1, known as the WW domain. The mutation substitutes tyrosine 65 with cysteine and is located within the conserved core of aromatic amino acids of the domain. We show here that the binding property of the Y65C-mutated WW domain and the full-length mutant protein toward its cognate proline-rich ligands was diminished. Furthermore, in GolabiIto-Hall-derived lymphoblasts we showed that the complex between PQBP1-Y65C and WBP11 (WW domain-binding protein 11) splicing factor was compromised. In these cells a substantial decrease in pre-mRNA splicing efficiency was detected. Our study points to the critical role of the WW domain in the function of the PQBP1 protein and provides an insight into the molecular mechanism that underlies the X chromosome-linked mental retardation entities classified globally as Renpenning syndrome.

show abstract

Allosteric modulation of the binding affinity between PQBP1 and the spliceosomal protein U5‐15kD

et al. 2016

View full text Add to dashboard Cite

Edited by Michael IbbaPolyglutamine tract-binding protein 1 (PQBP1) is an intrinsically disordered protein composed of a small folded WW domain and a long disordered region. PQBP1 binds to spliceosomal proteins WBP11 and U5-15kD through its N-terminal WW domain and C-terminal region, respectively. Here, we reveal that the binding between PQBP1 and WBP11 reduces the binding affinity between PQBP1 and U5-15kD. Our results suggest that the interaction between PQBP1 and WBP11 negatively modulates the U5-15kD binding of PQBP1 by an allosteric mechanism.

show abstract

SIPP1, a novel pre-mRNA splicing factor and interactor of protein phosphatase-1

Cited by 52 publications

References 40 publications

Structure and Function of the Two Tandem WW Domains of the Pre-mRNA Splicing Factor FBP21 (Formin-binding Protein 21)

Structure and Function of the Two Tandem WW Domains of the Pre-mRNA Splicing Factor FBP21 (Formin-binding Protein 21)

Y65C Missense Mutation in the WW Domain of the Golabi-Ito-Hall Syndrome Protein PQBP1 Affects Its Binding Activity and Deregulates Pre-mRNA Splicing

Allosteric modulation of the binding affinity between PQBP1 and the spliceosomal protein U5‐15kD

Contact Info

Product

Resources

About