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

K. D. Raczynska, M. D. Ruepp, A. Brzek, S. Reber, V. Romeo, B. Rindlisbacher, M. Heller, Z. Szweykowska-Kulinska, A. Jarmolowski, D. Schumperli

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)9711-9728
Number of pages18
JournalNucleic Acids Research
Volume43
Issue number20
DOIs
Publication statusPublished - 1 Nov 2015

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