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

Abstract

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 translational machinery. Finally we show that genes are also flanked by sense, 3' polyadenylated sRNAs that are likely to be capped.To date, all sequencing reports characterizing sRNAs rely on conversion of RNA into cDNA employing ligation and/or amplification steps 7 . These steps could introduce bias in detecting

Single Cell Analysis of RNA-mediated Histone H3.3 Recruitment to a Cytomegalovirus Promoter-regulated Transcription Site

“…Canonical RNA-dependent RNA polymerases are components of plant, nematode, and S. pombe RNA interference (RNAi) pathways (79), but they are thought to have been lost in the ancestor of animals (80). RNA exosome sequencing suggests, however, that RNAdependent RNA polymerase activity is also present in mammals because AS transcripts, which cross splice junctions and contain non-encoded 5Ј stretches of polyuridine, have been detected (71,81). TERT, the protein subunit of telomerase, is reported to function as an RNA-dependent RNA polymerase (82).…”

The Bromodomain protein BRD4 controls HOTAIR, a long noncoding RNA essential for glioblastoma proliferation

“…To date, lncRNA expression has not been extensively analyzed in GBM samples except in a few studies that used microarrays from TCGA and Gene Expression Omnibus (24,25). Although informative, such studies likely miss unannotated lncRNAs not represented on arrays and are often biased to polyadenylated fractions that contain fewer lncRNAs (26). We decided to use single molecule sequencing (SMS) to provide a sensitive (27) and accurate (28) signature of lncRNA dysregulated in GBM.…”

Downward causation by information control in micro-organisms

“…Therefore, it is the master function that ultimately 'decides' whether the information will be The diagram in (a) conceptualizes and summarizes the different pathways and feedback loops that relate to the three major categories of informational polymers involved in the COS. ncRNAs, non-coding RNAs; mRNAs, messenger RNAs (coding for proteins). RNA replication (step 6) is a process that occurs in eukaryotic cells [38,39]. It might also occur in bacteria.…”