A Genome-wide RNA Interference Screen Reveals that Variant Histones Are Necessary for Replication-Dependent Histone Pre-mRNA Processing

Eric Wagner, Brandon D. Burch, Ashley C. Godfrey, Harmony R. Salzler, Robert J. Duronio, William F. Marzluff

Research output: Contribution to journalArticle

59 Scopus citations


Metazoan replication-dependent histone mRNAs are not polyadenylated and instead end in a conserved stem loop that is the cis element responsible for coordinate posttranscriptional regulation of these mRNAs. Using biochemical approaches, only a limited number of factors required for cleavage of histone pre-mRNA have been identified. We therefore performed a genome-wide RNA interference screen in Drosophila cells using a GFP reporter that is expressed only when histone pre-mRNA processing is disrupted. Four of the 24 genes identified encode proteins also necessary for cleavage/polyadenylation, indicating mechanistic conservation in formation of different mRNA 3′ ends. We also unexpectedly identified the histone variants H2Av and H3.3A/B. In H2Av mutant cells, U7 snRNP remains active but fails to accumulate at the histone locus, suggesting there is a regulatory pathway that coordinates the production of variant and canonical histones that acts via localization of essential histone pre-mRNA processing factors.

Original languageEnglish (US)
Pages (from-to)692-699
Number of pages8
JournalMolecular Cell
Issue number4
StatePublished - Nov 30 2007
Externally publishedYes



  • RNA

ASJC Scopus subject areas

  • Molecular Biology

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