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