FUS/TLS contributes to replication-dependent histone gene expression by interaction with U7 snRNPs and histone-specific transcription factors

Nucleic Acids Res. 2015 Nov 16;43(20):9711-28. doi: 10.1093/nar/gkv794. Epub 2015 Aug 6.


Replication-dependent histone genes are up-regulated during the G1/S phase transition to meet the requirement for histones to package the newly synthesized DNA. In mammalian cells, this increment is achieved by enhanced transcription and 3' end processing. The non-polyadenylated histone mRNA 3' ends are generated by a unique mechanism involving the U7 small ribonucleoprotein (U7 snRNP). By using affinity purification methods to enrich U7 snRNA, we identified FUS/TLS as a novel U7 snRNP interacting protein. Both U7 snRNA and histone transcripts can be precipitated by FUS antibodies predominantly in the S phase of the cell cycle. Moreover, FUS depletion leads to decreased levels of correctly processed histone mRNAs and increased levels of extended transcripts. Interestingly, FUS antibodies also co-immunoprecipitate histone transcriptional activator NPAT and transcriptional repressor hnRNP UL1 in different phases of the cell cycle. We further show that FUS binds to histone genes in S phase, promotes the recruitment of RNA polymerase II and is important for the activity of histone gene promoters. Thus, FUS may serve as a linking factor that positively regulates histone gene transcription and 3' end processing by interacting with the U7 snRNP and other factors involved in replication-dependent histone gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle
  • Cell Cycle Proteins / metabolism
  • DNA Replication*
  • Gene Expression Regulation*
  • HEK293 Cells
  • HeLa Cells
  • Heterogeneous-Nuclear Ribonucleoproteins / metabolism
  • Histones / biosynthesis
  • Histones / genetics*
  • Humans
  • Nuclear Proteins / metabolism
  • Promoter Regions, Genetic
  • RNA, Small Nuclear / metabolism
  • RNA-Binding Protein FUS / metabolism*
  • Ribonucleoprotein, U7 Small Nuclear / metabolism*
  • Transcription Factors / metabolism
  • Transcription, Genetic*


  • Cell Cycle Proteins
  • HNRNPUL1 protein, human
  • Heterogeneous-Nuclear Ribonucleoproteins
  • Histones
  • NPAT protein, human
  • Nuclear Proteins
  • RNA, Small Nuclear
  • RNA-Binding Protein FUS
  • Ribonucleoprotein, U7 Small Nuclear
  • Transcription Factors
  • U7 small nuclear RNA