Expression of distinct RNAs from 3′ untranslated regions

Abstract

The 3′ untranslated regions (3′UTRs) of eukaryotic genes regulate mRNA stability, localization and translation. Here, we present evidence that large numbers of 3′UTRs in human, mouse and fly are also expressed separately from the associated protein-coding sequences to which they are normally linked, likely by post-transcriptional cleavage. Analysis of CAGE (capped analysis of gene expression), SAGE (serial analysis of gene expression) and cDNA libraries, as well as microarray expression profiles, demonstrate that the independent expression of 3′UTRs is a regulated and conserved genome-wide phenomenon. We characterize the expression of several 3′UTR-derived RNAs (uaRNAs) in detail in mouse embryos, showing by in situ hybridization that these transcripts are expressed in a cell- and subcellular-specific manner. Our results suggest that 3′UTR sequences can function not only in cis to regulate protein expression, but also intrinsically and independently in trans, likely as noncoding RNAs, a conclusion supported by a number of previous genetic studies. Our findings suggest novel functions for 3′UTRs, as well as caution in the use of 3′UTR sequence probes to analyze gene expression.

Hidden treasures in unspliced EST data

“…We frequently find that CAGE tags, i.e., markers for transcription start sites, are located within long unspliced 3'UTRs. This supports the observation in [12] that these 3'UTRs are also transcribed in an independent mode. 586,242 of the approximately 1.6 million CAGE tags overlap with a total of 41,136 unspliced EST clusters.…”

“…In line with the finding of ref. [12], a lot of these 3'UTR extensions contain a TSS for an independently transcribed uaRNA. We identify at least 25 likely uaRNAs with strong support from the CAGE data.…”

“…This independent expression of 3'UTR-derived RNAs (uaRNAs) is regulated and conserved. They appear to function as noncoding RNAs in trans [12]. In the form of independent uaRNAs, they are often detectable as unspliced ESTs.…”

Transcriptome Analysis of Non‐Coding RNAs in Livestock Species: Elucidating the Ambiguity

“…Some ncRNAs are processed into functionally important transcripts such as microRNA (miRNA), transfer RNA (tRNA), ribosomal RNA (rRNA), small nucleolar RNA (snoRNA), small nuclear RNA (snRNA), small interfering RNA (siRNA), PIWI-interacting RNA (piRNA), circular RNA (circRNA), long non-coding RNA (lncRNA) and several classes with limited information about their functions. In addition to the well described ncRNA classes, clusters of ncRNA (22-200 nucleotides (nt)) were detected at the 5, and 3′end of human and mouse genes, and named promoter-associated short RNAs (PASRs) and termini-associated short RNAs (TASRs) [1]. Mercer et al [2] described a class of ncRNA, about 50-200 nt, that are processed from the 3′UTRs of protein-coding genes (uaRNAs).…”

The role of non-coding RNAs in male sex determination and differentiation

“…Many lncRNAs are transcribed from intergenic regions (Guttman et al 2011, Ulitsky & Bartel 2013, so-called long intergenic ncRNAs (lincRNAs), but there are also numerous lncRNAs transcribed from the sense or antisense strand of protein-coding genes (Wu et al 2014). Some ncRNAs seem to be processed from 3 0 UTR of mRNAs (Mercer et al 2011), whereas intronic lncRNAs are part of an intron from another transcript (Carninci et al 2005, Consortium et al 2007). Many of these lncRNAs were believed to be by-products from transcription, splicing, RNA processing, etc., but more and more data emerge demonstrating specific expression and function of various lncRNAs (for review, see Fatica & Bozzoni (2014)).…”