First Evidence of RNA Copying Mechanisms in Human Cells

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Helicos Announces Nature Publication on First Evidence of RNA Copying Mechanisms in Human Cells

-- Joint Research with University of Pittsburgh School of Medicine, Integromics, Inc. and the University of Geneva Medical School --

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Helicos BioSciences Corporation (NASDAQ: HLCS) today announced a publication demonstrating the detection and quantification of novel small RNA molecules using Helicos’ single-molecule sequencing technology. These data confirm a long-held, unproven hypothesis that mammalian cells are capable of synthesizing RNA by copying RNA molecules directly. The findings are presented in a paper, entitled “New class of gene-termini-associated human RNAs suggests a novel RNA copying mechanism,” by Kapranov, et al, available today in Nature.

“This study supports our belief that Helicos’ tSMS technology provides the platform capability to identify and quantitate these RNAs and reinforces the potential clinical advantages of our single molecule-sequencing platform.”

“For the first time, we have evidence to support the hypothesis that human cells have the widespread ability to copy RNA as well as DNA,” said Bino John, Ph.D., assistant professor of computational biology, University of Pittsburgh School of Medicine. “These findings emphasize the complexity of human RNA populations and suggest the important role for single molecule-sequencing for accurate and comprehensive genetic profiling.”

Today’s Nature publication presents joint research findings, utilizing Helicos’ proprietary true Single Molecule Sequencing (tSMS™) technology to profile small RNAs from human cells and tissues. The study uncovered several new classes of RNAs that are produced by uncharacterized RNA copying mechanisms. Such RNA copying mechanisms have been well documented in plants and simple organisms, but this work provides the first supporting evidence for such a mechanism in human cells.

“This class of non-coding RNA molecules has been historically overlooked because available sequencing platforms are often unable to provide accurate detection and quantification,” commented Dr. Patrice Milos, Chief Scientific Officer at Helicos. “This study supports our belief that Helicos’ tSMS technology provides the platform capability to identify and quantitate these RNAs and reinforces the potential clinical advantages of our single molecule-sequencing platform.”

The Nature publication (Vol. 466, No. 7306) was co-authored by Drs. Bino John, A. Paula Monaghan and Sang Woo Kim, of the University of Pittsburgh School of Medicine; Dr. Sylvain Foissac from Integromics, Inc.; Drs. Stylianos Antonarakis and Christelle Borel of the University of Geneva Medical School and Drs. Philipp Kapranov, Doron Lipson, Fatih Ozsolak, Chris Hart, Steve Roels and Patrice Milos of Helicos BioSciences Corporation.

The work cited in this paper was funded by the American Cancer Society, the National Institutes of Health, the Swiss National Science Foundation, Integromics, Inc., and Helicos BioSciences Corporation.

Additional information can be found in Helicos' Annual Report on Form 10-K for the fiscal year ended December 31, 2009, as filed with the SEC on April 15, 2010, together with its Quarterly Report on Form 10-Q for the first fiscal quarter 2010, as filed with the SEC on May 17, 2010. These reports include a discussion regarding the company's need to raise capital to pursue its new business of developing molecular diagnostic tests, disclosures regarding the company's operational results and liquidity position, and additional disclosures regarding other risks and uncertainties faced by Helicos.

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http://www.nature.com/nature/journal...ture09190.html

Letter

Nature 466, 642-646 (29 July 2010) | doi:10.1038/nature09190; Received 2 July 2009; Accepted 20 May 2010

New class of gene-termini-associated human RNAs suggests a novel RNA copying mechanism

Philipp Kapranov1,6, Fatih Ozsolak1,6, Sang Woo Kim2,6, Sylvain Foissac3,6, Doron Lipson1, Chris Hart1, Steve Roels1, Christelle Borel4, Stylianos E. Antonarakis4, A. Paula Monaghan5, Bino John2 & Patrice M. Milos1

1. Helicos BioSciences Corporation, 1 Kendall Sq. Ste B7301 Cambridge, Massachusetts 02139-1671, USA
2. Department of Computational and Systems Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15260, USA
3. Integromics, S.L., Grisolía 2, 28760 Tres Cantos, Madrid, Spain
4. Department of Genetic Medicine and Development, University of Geneva Medical School, University of Geneva, 1 rue Michel-Servet, 1211 Geneva, Switzerland
5. Department of Neurobiology, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, Pennsylvania 15260, USA
6. These authors contributed equally to this work.

Correspondence to: Philipp Kapranov1,6 Email: philippk08@gmail.com

Correspondence to: Patrice M. Milos1 Email: pmilos@helicosbio.com

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Abstract

Small (<200 nucleotide) RNA (sRNA) profiling of human cells using various technologies demonstrates unexpected complexity of sRNAs with hundreds of thousands of sRNA species present1, 2, 3, 4. Genetic and in vitro studies show that these RNAs are not merely degradation products of longer transcripts but could indeed have a function1, 2, 5. Furthermore, profiling of RNAs, including the sRNAs, can reveal not only novel transcripts, but also make clear predictions about the existence and properties of novel biochemical pathways operating in a cell. For example, sRNA profiling in human cells indicated the existence of an unknown capping mechanism operating on cleaved RNA2, a biochemical component of which was later identified6. Here we show that human cells contain a novel type of sRNA that has non-genomically encoded 5′ poly(U) tails. The presence of these RNAs at the termini of genes, specifically at the very 3′ ends of known mRNAs, strongly argues for the presence of a yet uncharacterized endogenous biochemical pathway in cells that can copy RNA. We show that this pathway can operate on multiple genes, with specific enrichment towards transcript-encoding components of the translational machinery. Finally, we show that genes are also flanked by sense, 3′ polyadenylated sRNAs that are likely to be capped.

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