FRG1P-mediated aggregation of proteins involved in pre-mRNA processing

Silvana van Koningsbruggen, Kirsten R Straasheijm, Ellen Sterrenburg, Natascha de Graaf, Hans G Dauwerse, Rune R Frants, Silvère M van der Maarel

    Research output: Contribution to journalArticle

    40 Citations (Scopus)

    Abstract

    FRG1 is considered a candidate gene for facioscapulohumeral muscular dystrophy (FSHD) based on its location at chromosome 4qter and its upregulation in FSHD muscle. The FRG1 protein (FRG1P) localizes to nucleoli, Cajal bodies (and speckles), and has been suggested to be a component of the human spliceosome but its exact function is unknown. Recently, transgenic mice overexpressing high levels of FRG1P in skeletal muscle were described to present with muscular dystrophy. Moreover, upregulation of FRG1P was demonstrated to correlate with missplicing of specific pre-mRNAs. In this study, we have combined colocalization studies with yeast two-hybrid screens to identify proteins that associate with FRG1P. We demonstrate that artificially induced nucleolar aggregates of VSV-FRG1P specifically sequester proteins involved in pre-mRNA processing. In addition, we have identified SMN, PABPN1, and FAM71B, a novel speckle and Cajal body protein, as binding partners of FRG1P. All these proteins are, or seem to be, involved in RNA biogenesis. Our data confirm the presence of FRG1P in protein complexes containing human spliceosomes and support a potential role of FRG1P in either splicing or another step in nuclear RNA biogenesis. Intriguingly, among FRG1P-associated proteins are SMN and PABPN1, both being involved in neuromuscular disorders, possibly through RNA biogenesis-related processes.
    Original languageEnglish
    Pages (from-to)53-64
    Number of pages12
    JournalChromosoma
    Volume116
    Issue number1
    DOIs
    Publication statusPublished - 2007

    Fingerprint

    RNA Precursors
    Proteins
    Facioscapulohumeral Muscular Dystrophy
    Spliceosomes
    Up-Regulation
    RNA
    Nuclear RNA
    Muscular Dystrophies
    Protein Binding
    Transgenic Mice
    Skeletal Muscle

    Keywords

    • Alternative Splicing
    • Animals
    • Cell Line
    • Cell Nucleolus
    • Humans
    • Immunoprecipitation
    • Muscular Dystrophy, Facioscapulohumeral
    • Nuclear Proteins
    • Proteins
    • RNA Precursors
    • RNA Processing, Post-Transcriptional
    • Recombinant Proteins
    • Troponin T
    • Two-Hybrid System Techniques

    Cite this

    van Koningsbruggen, S., Straasheijm, K. R., Sterrenburg, E., de Graaf, N., Dauwerse, H. G., Frants, R. R., & van der Maarel, S. M. (2007). FRG1P-mediated aggregation of proteins involved in pre-mRNA processing. Chromosoma, 116(1), 53-64. https://doi.org/10.1007/s00412-006-0083-3
    van Koningsbruggen, Silvana ; Straasheijm, Kirsten R ; Sterrenburg, Ellen ; de Graaf, Natascha ; Dauwerse, Hans G ; Frants, Rune R ; van der Maarel, Silvère M. / FRG1P-mediated aggregation of proteins involved in pre-mRNA processing. In: Chromosoma. 2007 ; Vol. 116, No. 1. pp. 53-64.
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    abstract = "FRG1 is considered a candidate gene for facioscapulohumeral muscular dystrophy (FSHD) based on its location at chromosome 4qter and its upregulation in FSHD muscle. The FRG1 protein (FRG1P) localizes to nucleoli, Cajal bodies (and speckles), and has been suggested to be a component of the human spliceosome but its exact function is unknown. Recently, transgenic mice overexpressing high levels of FRG1P in skeletal muscle were described to present with muscular dystrophy. Moreover, upregulation of FRG1P was demonstrated to correlate with missplicing of specific pre-mRNAs. In this study, we have combined colocalization studies with yeast two-hybrid screens to identify proteins that associate with FRG1P. We demonstrate that artificially induced nucleolar aggregates of VSV-FRG1P specifically sequester proteins involved in pre-mRNA processing. In addition, we have identified SMN, PABPN1, and FAM71B, a novel speckle and Cajal body protein, as binding partners of FRG1P. All these proteins are, or seem to be, involved in RNA biogenesis. Our data confirm the presence of FRG1P in protein complexes containing human spliceosomes and support a potential role of FRG1P in either splicing or another step in nuclear RNA biogenesis. Intriguingly, among FRG1P-associated proteins are SMN and PABPN1, both being involved in neuromuscular disorders, possibly through RNA biogenesis-related processes.",
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    van Koningsbruggen, S, Straasheijm, KR, Sterrenburg, E, de Graaf, N, Dauwerse, HG, Frants, RR & van der Maarel, SM 2007, 'FRG1P-mediated aggregation of proteins involved in pre-mRNA processing', Chromosoma, vol. 116, no. 1, pp. 53-64. https://doi.org/10.1007/s00412-006-0083-3

    FRG1P-mediated aggregation of proteins involved in pre-mRNA processing. / van Koningsbruggen, Silvana; Straasheijm, Kirsten R; Sterrenburg, Ellen; de Graaf, Natascha; Dauwerse, Hans G; Frants, Rune R; van der Maarel, Silvère M.

    In: Chromosoma, Vol. 116, No. 1, 2007, p. 53-64.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - FRG1P-mediated aggregation of proteins involved in pre-mRNA processing

    AU - van Koningsbruggen, Silvana

    AU - Straasheijm, Kirsten R

    AU - Sterrenburg, Ellen

    AU - de Graaf, Natascha

    AU - Dauwerse, Hans G

    AU - Frants, Rune R

    AU - van der Maarel, Silvère M

    PY - 2007

    Y1 - 2007

    N2 - FRG1 is considered a candidate gene for facioscapulohumeral muscular dystrophy (FSHD) based on its location at chromosome 4qter and its upregulation in FSHD muscle. The FRG1 protein (FRG1P) localizes to nucleoli, Cajal bodies (and speckles), and has been suggested to be a component of the human spliceosome but its exact function is unknown. Recently, transgenic mice overexpressing high levels of FRG1P in skeletal muscle were described to present with muscular dystrophy. Moreover, upregulation of FRG1P was demonstrated to correlate with missplicing of specific pre-mRNAs. In this study, we have combined colocalization studies with yeast two-hybrid screens to identify proteins that associate with FRG1P. We demonstrate that artificially induced nucleolar aggregates of VSV-FRG1P specifically sequester proteins involved in pre-mRNA processing. In addition, we have identified SMN, PABPN1, and FAM71B, a novel speckle and Cajal body protein, as binding partners of FRG1P. All these proteins are, or seem to be, involved in RNA biogenesis. Our data confirm the presence of FRG1P in protein complexes containing human spliceosomes and support a potential role of FRG1P in either splicing or another step in nuclear RNA biogenesis. Intriguingly, among FRG1P-associated proteins are SMN and PABPN1, both being involved in neuromuscular disorders, possibly through RNA biogenesis-related processes.

    AB - FRG1 is considered a candidate gene for facioscapulohumeral muscular dystrophy (FSHD) based on its location at chromosome 4qter and its upregulation in FSHD muscle. The FRG1 protein (FRG1P) localizes to nucleoli, Cajal bodies (and speckles), and has been suggested to be a component of the human spliceosome but its exact function is unknown. Recently, transgenic mice overexpressing high levels of FRG1P in skeletal muscle were described to present with muscular dystrophy. Moreover, upregulation of FRG1P was demonstrated to correlate with missplicing of specific pre-mRNAs. In this study, we have combined colocalization studies with yeast two-hybrid screens to identify proteins that associate with FRG1P. We demonstrate that artificially induced nucleolar aggregates of VSV-FRG1P specifically sequester proteins involved in pre-mRNA processing. In addition, we have identified SMN, PABPN1, and FAM71B, a novel speckle and Cajal body protein, as binding partners of FRG1P. All these proteins are, or seem to be, involved in RNA biogenesis. Our data confirm the presence of FRG1P in protein complexes containing human spliceosomes and support a potential role of FRG1P in either splicing or another step in nuclear RNA biogenesis. Intriguingly, among FRG1P-associated proteins are SMN and PABPN1, both being involved in neuromuscular disorders, possibly through RNA biogenesis-related processes.

    KW - Alternative Splicing

    KW - Animals

    KW - Cell Line

    KW - Cell Nucleolus

    KW - Humans

    KW - Immunoprecipitation

    KW - Muscular Dystrophy, Facioscapulohumeral

    KW - Nuclear Proteins

    KW - Proteins

    KW - RNA Precursors

    KW - RNA Processing, Post-Transcriptional

    KW - Recombinant Proteins

    KW - Troponin T

    KW - Two-Hybrid System Techniques

    U2 - 10.1007/s00412-006-0083-3

    DO - 10.1007/s00412-006-0083-3

    M3 - Article

    VL - 116

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    JO - Chromosoma

    JF - Chromosoma

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    van Koningsbruggen S, Straasheijm KR, Sterrenburg E, de Graaf N, Dauwerse HG, Frants RR et al. FRG1P-mediated aggregation of proteins involved in pre-mRNA processing. Chromosoma. 2007;116(1):53-64. https://doi.org/10.1007/s00412-006-0083-3