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Elife. 2014 Aug 12;3:e03254. doi: 10.7554/eLife.03254.

A long non-coding RNA is required for targeting centromeric protein A to the human centromere.

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1
Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research,National Cancer Institute, Bethesda, United States.

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.

KEYWORDS:

CENP-A; centromeres; chromatin; epigenetics; histone variants; lncRNA

PMID:
25117489
PMCID:
PMC4145801
DOI:
10.7554/eLife.03254
[Indexed for MEDLINE]
Free PMC Article

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