Raf1 is a DCAF for the Rik1 DDB1-like protein and has separable roles in siRNA generation and chromatin modification

A. Buscaino, S.A. White, D.R. Houston, E. Lejeune, F. Simmer, F. de Lima Alves, P.T. Diyora, E.H. Bayne, J. Rappsilber, R.C. Allshire, T. Urano

    Research output: Contribution to journalArticle

    15 Citations (Scopus)

    Abstract

    Non-coding transcription can trigger histone post-translational modifications forming specialized chromatin. In fission yeast, heterochromatin formation requires RNAi and the histone H3K9 methyltransferase complex CLRC, composed of Clr4, Raf1, Raf2, Cul4, and Rik1. CLRC mediates H3K9 methylation and siRNA production; it also displays E3-ubiquitin ligase activity in vitro. DCAFs act as substrate receptors for E3 ligases and may couple ubiquitination with histone methylation. Here, structural alignment and mutation of signature WDxR motifs in Raf1 indicate that it is a DCAF for CLRC. We demonstrate that Raf1 promotes H3K9 methylation and siRNA amplification via two distinct, separable functions. The association of the DCAF Raf1 with Cul4-Rik1 is critical for H3K9 methylation, but dispensable for processing of centromeric transcripts into siRNAs. Thus the association of a DCAF, Raf1, with its adaptor, Rik1, is required for histone methylation and to allow RNAi to signal to chromatin.
    Original languageEnglish
    Article numbere1002499
    JournalPLoS Genetics
    Volume8
    Issue number2
    DOIs
    Publication statusPublished - 2012

    Fingerprint

    methylation
    small interfering RNA
    Methylation
    Small Interfering RNA
    Chromatin
    chromatin
    histones
    protein
    Histones
    Ubiquitin-Protein Ligases
    RNA Interference
    Proteins
    proteins
    ubiquitin-protein ligase
    Heterochromatin
    Schizosaccharomyces
    Schizosaccharomyces pombe
    Ubiquitination
    post-translational modification
    methyltransferases

    Cite this

    Buscaino, A., White, S. A., Houston, D. R., Lejeune, E., Simmer, F., de Lima Alves, F., ... Urano, T. (2012). Raf1 is a DCAF for the Rik1 DDB1-like protein and has separable roles in siRNA generation and chromatin modification. PLoS Genetics, 8(2), [e1002499]. https://doi.org/10.1371/journal.pgen.1002499
    Buscaino, A. ; White, S.A. ; Houston, D.R. ; Lejeune, E. ; Simmer, F. ; de Lima Alves, F. ; Diyora, P.T. ; Bayne, E.H. ; Rappsilber, J. ; Allshire, R.C. ; Urano, T. / Raf1 is a DCAF for the Rik1 DDB1-like protein and has separable roles in siRNA generation and chromatin modification. In: PLoS Genetics. 2012 ; Vol. 8, No. 2.
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    abstract = "Non-coding transcription can trigger histone post-translational modifications forming specialized chromatin. In fission yeast, heterochromatin formation requires RNAi and the histone H3K9 methyltransferase complex CLRC, composed of Clr4, Raf1, Raf2, Cul4, and Rik1. CLRC mediates H3K9 methylation and siRNA production; it also displays E3-ubiquitin ligase activity in vitro. DCAFs act as substrate receptors for E3 ligases and may couple ubiquitination with histone methylation. Here, structural alignment and mutation of signature WDxR motifs in Raf1 indicate that it is a DCAF for CLRC. We demonstrate that Raf1 promotes H3K9 methylation and siRNA amplification via two distinct, separable functions. The association of the DCAF Raf1 with Cul4-Rik1 is critical for H3K9 methylation, but dispensable for processing of centromeric transcripts into siRNAs. Thus the association of a DCAF, Raf1, with its adaptor, Rik1, is required for histone methylation and to allow RNAi to signal to chromatin.",
    author = "A. Buscaino and S.A. White and D.R. Houston and E. Lejeune and F. Simmer and {de Lima Alves}, F. and P.T. Diyora and E.H. Bayne and J. Rappsilber and R.C. Allshire and T. Urano",
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    language = "English",
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    Buscaino, A, White, SA, Houston, DR, Lejeune, E, Simmer, F, de Lima Alves, F, Diyora, PT, Bayne, EH, Rappsilber, J, Allshire, RC & Urano, T 2012, 'Raf1 is a DCAF for the Rik1 DDB1-like protein and has separable roles in siRNA generation and chromatin modification', PLoS Genetics, vol. 8, no. 2, e1002499. https://doi.org/10.1371/journal.pgen.1002499

    Raf1 is a DCAF for the Rik1 DDB1-like protein and has separable roles in siRNA generation and chromatin modification. / Buscaino, A.; White, S.A.; Houston, D.R.; Lejeune, E.; Simmer, F.; de Lima Alves, F.; Diyora, P.T.; Bayne, E.H.; Rappsilber, J.; Allshire, R.C.; Urano, T.

    In: PLoS Genetics, Vol. 8, No. 2, e1002499, 2012.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Raf1 is a DCAF for the Rik1 DDB1-like protein and has separable roles in siRNA generation and chromatin modification

    AU - Buscaino, A.

    AU - White, S.A.

    AU - Houston, D.R.

    AU - Lejeune, E.

    AU - Simmer, F.

    AU - de Lima Alves, F.

    AU - Diyora, P.T.

    AU - Bayne, E.H.

    AU - Rappsilber, J.

    AU - Allshire, R.C.

    AU - Urano, T.

    N1 - Copyright 2012 Elsevier B.V., All rights reserved.

    PY - 2012

    Y1 - 2012

    N2 - Non-coding transcription can trigger histone post-translational modifications forming specialized chromatin. In fission yeast, heterochromatin formation requires RNAi and the histone H3K9 methyltransferase complex CLRC, composed of Clr4, Raf1, Raf2, Cul4, and Rik1. CLRC mediates H3K9 methylation and siRNA production; it also displays E3-ubiquitin ligase activity in vitro. DCAFs act as substrate receptors for E3 ligases and may couple ubiquitination with histone methylation. Here, structural alignment and mutation of signature WDxR motifs in Raf1 indicate that it is a DCAF for CLRC. We demonstrate that Raf1 promotes H3K9 methylation and siRNA amplification via two distinct, separable functions. The association of the DCAF Raf1 with Cul4-Rik1 is critical for H3K9 methylation, but dispensable for processing of centromeric transcripts into siRNAs. Thus the association of a DCAF, Raf1, with its adaptor, Rik1, is required for histone methylation and to allow RNAi to signal to chromatin.

    AB - Non-coding transcription can trigger histone post-translational modifications forming specialized chromatin. In fission yeast, heterochromatin formation requires RNAi and the histone H3K9 methyltransferase complex CLRC, composed of Clr4, Raf1, Raf2, Cul4, and Rik1. CLRC mediates H3K9 methylation and siRNA production; it also displays E3-ubiquitin ligase activity in vitro. DCAFs act as substrate receptors for E3 ligases and may couple ubiquitination with histone methylation. Here, structural alignment and mutation of signature WDxR motifs in Raf1 indicate that it is a DCAF for CLRC. We demonstrate that Raf1 promotes H3K9 methylation and siRNA amplification via two distinct, separable functions. The association of the DCAF Raf1 with Cul4-Rik1 is critical for H3K9 methylation, but dispensable for processing of centromeric transcripts into siRNAs. Thus the association of a DCAF, Raf1, with its adaptor, Rik1, is required for histone methylation and to allow RNAi to signal to chromatin.

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    U2 - 10.1371/journal.pgen.1002499

    DO - 10.1371/journal.pgen.1002499

    M3 - Article

    VL - 8

    JO - PLoS Genetics

    JF - PLoS Genetics

    SN - 1553-7390

    IS - 2

    M1 - e1002499

    ER -