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J. Biol. Chem., Vol. 283, Issue 9, 5692-5698, February 29, 2008

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Nuclear Non-coding RNAs Are Transcribed from the Centromeres of Plasmodium falciparum and Are Associated with Centromeric Chromatin^*

Felomena Li, Lakshmi Sonbuchner¹, Sue A. Kyes, Christian Epp², and Kirk W. Deitsch, Stavros S. Niarchos Scholar³

From the Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, New York 10021 and the Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9D5, United Kingdom

Non-coding RNAs (ncRNAs) play an important role in a variety of nuclear processes, including genetic imprinting, RNA interference-mediated transcriptional repression, and dosage compensation. These transcripts are thought to influence chromosome organization and, in some cases, gene expression by directing the assembly of specific chromatin modifications to targeted regions of the genome. In the malaria parasite Plasmodium falciparum, little is known about the regulation of nuclear organization or gene expression, although a notable scarcity of identifiable transcription factors encoded in its genome has led to speculation that this organism may be unusually reliant on chromatin modifications as a mechanism for regulating gene expression. To study the mechanisms that regulate chromatin structure in malaria parasites, we examined the role of ncRNAs in the assembly of chromatin at the centromeres of P. falciparum. We show that centromeric regions within the Plasmodium genome contain bidirectional promoter activity driving the expression of short ncRNAs that are localized within the nucleus and appear to associate with the centromeres themselves, strongly suggesting that they are central characters in the maintenance and function of centromeric chromatin. These observations support the hypothesis that ncRNAs play an important role in the proper organizational assembly of chromatin in P. falciparum, perhaps compensating for a lack of both regulatory transcription factors and RNA interference machinery.

Received for publication, August 31, 2007 , and in revised form, December 21, 2007.

^* This work was supported in part by National Institutes of Health Grant AI 52390 and a grant from the Ellison Medical Foundation. The Department of Microbiology and Immunology at the Weill Medical College of Cornell University is supported by the William Randolph Hearst Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement"in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Student of the Weill Cornell/Rockefeller/Sloan-Kettering Tri-Institutional M.D.-Ph.D. Program. Supported by National Institutes of Health Medical Scientist Training Program Grant GM07739.

² Present address: Fraunhofer IME, Forckenbeckstr. 6, 52074 Aachen, Germany.

³ To whom correspondence should be addressed: Dept. of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Ave., Box 62, New York, NY 10021. Tel.: 212-746-4976; Fax: 212-746-4028; E-mail: kwd2001{at}med.cornell.edu.

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