Novel class of human RNAs associated with gene termini suggests an uncharacterized RNA copying mechanism

Short (< 200 nt) RNA (sRNA) profiling of human cells using various technologies demonstrates unexpected complexity of sRNAs with 100’s of thousands of sRNA species present 1 ,2,3,4. Genetic and in vitro studies argue that these RNAs are not merely degradation products of longer transcripts but could indeed have function 1 , 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, short RNA profiling in human cells suggested existence of an unknown capping mechanism operating on cleaved RNA 2 a biochemical component of which was later identified 6 . Here we show that human cells contain a novel type of sRNAs that have non-genomically encoded 5’ polyU tails. 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 a cell that can copy RNA. We show that this pathway can operate on multiple genes, with specific enrichment towards transcripts encoding components of the