Concentrating pre-mRNA processing factors in the histone locus body facilitates efficient histone mRNA biogenesis.

Autor:	Tatomer DC; Department of Biology, University of North Carolina, Chapel Hill, NC 27599., Terzo E; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599., Curry KP; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599., Salzler H; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599., Sabath I; Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599., Zapotoczny G; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599., McKay DJ; Department of Biology, University of North Carolina, Chapel Hill, NC 27599 Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC 27599 Department of Genetics, University of North Carolina, Chapel Hill, NC 27599., Dominski Z; Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599 Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC 27599., Marzluff WF; Department of Biology, University of North Carolina, Chapel Hill, NC 27599 Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599 Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599 Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC 27599 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599 marzluff@med.unc.edu duronio@med.unc.edu., Duronio RJ; Department of Biology, University of North Carolina, Chapel Hill, NC 27599 Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, NC 27599 Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, NC 27599 Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599 Department of Genetics, University of North Carolina, Chapel Hill, NC 27599 marzluff@med.unc.edu duronio@med.unc.edu.
Jazyk:	angličtina
Zdroj:	The Journal of cell biology [J Cell Biol] 2016 Jun 06; Vol. 213 (5), pp. 557-70. Date of Electronic Publication: 2016 May 30.
DOI:	10.1083/jcb.201504043
Abstrakt:	The histone locus body (HLB) assembles at replication-dependent histone genes and concentrates factors required for histone messenger RNA (mRNA) biosynthesis. FLASH (Flice-associated huge protein) and U7 small nuclear RNP (snRNP) are HLB components that participate in 3' processing of the nonpolyadenylated histone mRNAs by recruiting the endonuclease CPSF-73 to histone pre-mRNA. Using transgenes to complement a FLASH mutant, we show that distinct domains of FLASH involved in U7 snRNP binding, histone pre-mRNA cleavage, and HLB localization are all required for proper FLASH function in vivo. By genetically manipulating HLB composition using mutations in FLASH, mutations in the HLB assembly factor Mxc, or depletion of the variant histone H2aV, we find that failure to concentrate FLASH and/or U7 snRNP in the HLB impairs histone pre-mRNA processing. This failure results in accumulation of small amounts of polyadenylated histone mRNA and nascent read-through transcripts at the histone locus. Thus, the HLB concentrates FLASH and U7 snRNP, promoting efficient histone mRNA biosynthesis and coupling 3' end processing with transcription termination. (© 2016 Tatomer et al.)
Databáze:	MEDLINE
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