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

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

Author information

1
Institute of Cell Biology, University of Bern, Bern, Switzerland Department of Gene Expression, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznan, Poland doracz@amu.edu.pl.
2
Institute of Cell Biology, University of Bern, Bern, Switzerland Department of Chemistry and Biochemistry, University of Bern, Bern, Switzerland marc.ruepp@dcb.unibe.ch.
3
Department of Gene Expression, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznan, Poland.
4
Department of Chemistry and Biochemistry, University of Bern, Bern, Switzerland Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
5
Institute of Cell Biology, University of Bern, Bern, Switzerland Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
6
Institute of Cell Biology, University of Bern, Bern, Switzerland.
7
Department of Clinical Research, University of Bern, Bern, Switzerland.
8
Institute of Cell Biology, University of Bern, Bern, Switzerland daniel.schuemperli@izb.unibe.ch.

Abstract

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.

PMID:
26250115
PMCID:
PMC4787759
DOI:
10.1093/nar/gkv794
[Indexed for MEDLINE]
Free PMC Article

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