title: Coordinating cell cycle-regulated histone gene expression through assembly and function of the Histone Locus Body.
abstract: Metazoan replication-dependent (RD) histone genes encode the only known cellular mRNAs that are not polyadenylated. These mRNAs end instead in a conserved stem-loop, which is formed by an endonucleolytic cleavage of the pre-mRNA. The genes for all 5 histone proteins are clustered in all metazoans and coordinately regulated with high levels of expression during S phase. Production of histone mRNAs occurs in a nuclear body called the Histone Locus Body (HLB), a subdomain of the nucleus defined by a concentration of factors necessary for histone gene transcription and pre-mRNA processing. These factors include the scaffolding protein NPAT, essential for histone gene transcription, and FLASH and U7 snRNP, both essential for histone pre-mRNA processing. Histone gene expression is activated by Cyclin E/Cdk2-mediated phosphorylation of NPAT at the G1-S transition. The concentration of factors within the HLB couples transcription with pre-mRNA processing, enhancing the efficiency of histone mRNA biosynthesis.
authors.affiliation: a Department of Biology , University of North Carolina , Chapel Hill , NC , USA.|b Department of Genetics , University of North Carolina , Chapel Hill , NC , USA.|c Integrative Program for Biological and Genome Sciences , University of North Carolina , Chapel Hill , NC , USA.|d Lineberger Comprehensive Cancer Center , University of North Carolina , Chapel Hill , NC , USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Duronio
authors.affiliation: a Department of Biology , University of North Carolina , Chapel Hill , NC , USA.|c Integrative Program for Biological and Genome Sciences , University of North Carolina , Chapel Hill , NC , USA.|d Lineberger Comprehensive Cancer Center , University of North Carolina , Chapel Hill , NC , USA.|e Department of Biochemistry and Biophysics , University of North Carolina , Chapel Hill , NC , USA.
authors.forename: William F
authors.initials: WF
authors.lastname: Marzluff
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D020541:Coiled Bodies / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D011485:Protein Binding; D012322:RNA Precursors / Q000235:genetics / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012342:RNA, Small Nuclear / Q000235:genetics / Q000378:metabolism; D020885:Ribonucleoprotein, U7 Small Nuclear / Q000378:metabolism
chemical_list: D006657:Histones; D012322:RNA Precursors; D012333:RNA, Messenger; D012342:RNA, Small Nuclear; D020885:Ribonucleoprotein, U7 Small Nuclear
keywords: Cell cycle; Drosophila; histone genes; mRNA processing; nuclear body