title: FUS/TLS contributes to replication-dependent histone gene expression by interaction with U7 snRNPs and histone-specific transcription factors.
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.
authors.affiliation: 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.
authors.forename: Katarzyna Dorota
authors.initials: KD
authors.lastname: Raczynska
authors.affiliation: Institute of Cell Biology, University of Bern, Bern, Switzerland Department of Chemistry and Biochemistry, University of Bern, Bern, Switzerland marc.ruepp@dcb.unibe.ch.
authors.forename: Marc-David
authors.initials: MD
authors.lastname: Ruepp
authors.affiliation: Department of Gene Expression, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznan, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Brzek
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, Bern, Switzerland Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Reber
authors.affiliation: Institute of Cell Biology, University of Bern, Bern, Switzerland Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
authors.forename: Valentina
authors.initials: V
authors.lastname: Romeo
authors.affiliation: Institute of Cell Biology, University of Bern, Bern, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Rindlisbacher
authors.affiliation: Department of Clinical Research, University of Bern, Bern, Switzerland.
authors.forename: Manfred
authors.initials: M
authors.lastname: Heller
authors.affiliation: Department of Gene Expression, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznan, Poland.
authors.forename: Zofia
authors.initials: Z
authors.lastname: Szweykowska-Kulinska
authors.affiliation: Department of Gene Expression, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, Poznan, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Jarmolowski
authors.affiliation: Institute of Cell Biology, University of Bern, Bern, Switzerland daniel.schuemperli@izb.unibe.ch.
authors.forename: Daniel
authors.initials: D
authors.lastname: Schümperli
mesh_terms: D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism; D004261:DNA Replication; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006367:HeLa Cells; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism; D006657:Histones / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012342:RNA, Small Nuclear / Q000378:metabolism; D034702:RNA-Binding Protein FUS / Q000378:metabolism*; D020885:Ribonucleoprotein, U7 Small Nuclear / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D018797:Cell Cycle Proteins; C475078:HNRNPUL1 protein, human; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006657:Histones; C101693:NPAT protein, human; D009687:Nuclear Proteins; D012342:RNA, Small Nuclear; D034702:RNA-Binding Protein FUS; D020885:Ribonucleoprotein, U7 Small Nuclear; D014157:Transcription Factors; C405487:U7 small nuclear RNA