HP1(Swi6) mediates the recognition and destruction of heterochromatic RNA transcripts.
HP1 proteins are major components of heterochromatin, which is generally perceived to be an inert and transcriptionally inactive chromatin structure. Yet, HP1 binding to chromatin is highly dynamic and robust silencing of heterochromatic genes can involve RNA processing. Here, we demonstrate by a combination of in vivo and in vitro experiments that the fission yeast HP1(Swi6) protein guarantees tight repression of heterochromatic genes through RNA sequestration and degradation. Stimulated by positively charged residues in the hinge region, RNA competes with methylated histone H3K9 for binding to the chromodomain of HP1(Swi6). Hence, HP1(Swi6) binding to RNA is incompatible with stable heterochromatin association. We propose a model in which an ensemble of HP1(Swi6) proteins functions as a heterochromatin-specific checkpoint, capturing and priming heterochromatic RNAs for the RNA degradation machinery. Sustaining a functional checkpoint requires continuous exchange of HP1(Swi6) within heterochromatin, which explains the dynamic localization of HP1 proteins on heterochromatin.
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Claudia
C
Keller
Ricardo
R
Adaixo
Rieka
R
Stunnenberg
Katrina J
KJ
Woolcock
Sebastian
S
Hiller
Marc
M
Bühler
D000595:Amino Acid Sequence; D002843:Chromatin / Q000737:chemistry; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D020868:Gene Silencing; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006570:Heterochromatin / Q000737:chemistry* / Q000378:metabolism; D006657:Histones / Q000737:chemistry; D008745:Methylation; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011132:Polyribosomes / Q000737:chemistry; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012261:Ribonucleoproteins / Q000737:chemistry; D012568:Schizosaccharomyces / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000235:genetics*
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006570:Heterochromatin; D006657:Histones; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D029702:Schizosaccharomyces pombe Proteins; C465958:Swi6 protein, S pombe; D049452:Green Fluorescent Proteins; D012313:RNA