%0 Journal Article %J Mol Cell %D 2007 %T A genome-wide RNA interference screen reveals that variant histones are necessary for replication-dependent histone pre-mRNA processing. %A Wagner, Eric J %A Burch, Brandon D %A Godfrey, Ashley C %A Salzler, Harmony R %A Duronio, Robert J %A Marzluff, William F %K Animals %K Base Sequence %K DNA Replication %K drosophila melanogaster %K Drosophila Proteins %K Genes, Reporter %K Genome, Insect %K Histones %K Molecular Sequence Data %K Mutant Proteins %K Polyadenylation %K Protein Transport %K Ribonucleoprotein, U7 Small Nuclear %K RNA Interference %K RNA Precursors %K RNA Processing, Post-Transcriptional %X

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.

%B Mol Cell %V 28 %P 692-9 %8 2007 Nov 30 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/18042462?dopt=Abstract %R 10.1016/j.molcel.2007.10.009