CPF Recruitment to Non-canonical Transcription Termination Sites Triggers Heterochromatin Assembly and Gene Silencing

Cell Rep. 2019 Jul 2;28(1):267-281.e5. doi: 10.1016/j.celrep.2019.05.107.


In eukaryotic genomes, heterochromatin is targeted by RNAi machinery and/or by pathways requiring RNA elimination and transcription termination factors. However, a direct connection between termination machinery and RNA polymerase II (RNAPII) transcriptional activity at heterochromatic loci has remained elusive. Here, we show that, in fission yeast, the conserved cleavage and polyadenylation factor (CPF) is a key component involved in RNAi-independent assembly of constitutive and facultative heterochromatin domains and that CPF is broadly required to silence genes regulated by Clr4SUV39H. Remarkably, CPF is recruited to non-canonical termination sites within the body of genes by the YTH family RNA-binding protein Mmi1 and is required for RNAPII transcription termination and facultative heterochromatin assembly. CPF loading by Mmi1 also promotes the selective termination of long non-coding RNAs that regulate gene expression in cis. These analyses delineate a mechanism in which CPF loaded onto non-canonical termination sites specifies targets of heterochromatin assembly and gene silencing.

Keywords: CPF; Mmi1; RNA polymerase II; YTH; facultative; gene silencing; heterochromatin; histone methylation; pre-mRNA processing; transcription termination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chromatin Assembly and Disassembly / genetics
  • Exoribonucleases / genetics
  • Exoribonucleases / metabolism
  • Gene Expression Regulation, Fungal
  • Gene Silencing*
  • Heterochromatin / metabolism*
  • Histone-Lysine N-Methyltransferase / genetics
  • Histone-Lysine N-Methyltransferase / metabolism
  • Meiosis / genetics
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism
  • RNA Interference
  • RNA Polymerase II / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / metabolism
  • Schizosaccharomyces pombe Proteins / genetics
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Transcription Termination, Genetic*
  • mRNA Cleavage and Polyadenylation Factors / genetics
  • mRNA Cleavage and Polyadenylation Factors / metabolism*


  • Cell Cycle Proteins
  • Heterochromatin
  • Mmi1 protein, S pombe
  • RNA, Long Noncoding
  • Schizosaccharomyces pombe Proteins
  • mRNA Cleavage and Polyadenylation Factors
  • Histone-Lysine N-Methyltransferase
  • clr4 protein, S pombe
  • RNA Polymerase II
  • Exoribonucleases
  • dhp1protein, S pombe
  • Phosphoprotein Phosphatases
  • ssu72 protein, S pombe