title: A long non-coding RNA is required for targeting centromeric protein A to the human centromere.
abstract: The centromere is a specialized chromatin region marked by the histone H3 variant CENP-A. Although active centromeric transcription has been documented for over a decade, the role of centromeric transcription or transcripts has been elusive. Here, we report that centromeric α-satellite transcription is dependent on RNA Polymerase II and occurs at late mitosis into early G1, concurrent with the timing of new CENP-A assembly. Inhibition of RNA Polymerase II-dependent transcription abrogates the recruitment of CENP-A and its chaperone HJURP to native human centromeres. Biochemical characterization of CENP-A associated RNAs reveals a 1.3 kb molecule that originates from centromeres, which physically interacts with the soluble pre-assembly HJURP/CENP-A complex in vivo, and whose down-regulation leads to the loss of CENP-A and HJURP at centromeres. This study describes a novel function for human centromeric long non-coding RNAs in the recruitment of HJURP and CENP-A, implicating RNA-based chaperone targeting in histone variant assembly.
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research,National Cancer Institute, Bethesda, United States.
authors.forename: Delphine
authors.initials: D
authors.lastname: Quénet
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research,National Cancer Institute, Bethesda, United States.
authors.forename: Yamini
authors.initials: Y
authors.lastname: Dalal
mesh_terms: D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D002503:Centromere / Q000737:chemistry / Q000378:metabolism*; D000076247:Centromere Protein A; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008938:Mitosis; D011485:Protein Binding; D021381:Protein Transport; D012319:RNA Polymerase II / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C524371:HJURP protein, human; D006657:Histones; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D012319:RNA Polymerase II
keywords: CENP-A; centromeres; chromatin; epigenetics; histone variants; lncRNA