Dark Matter Transcripts: Sound and Fury, Signifying Nothing?

Abstract

Transcript profiles around genes are rendered as a sound wave.

The Vast, Conserved Mammalian lincRNome

“…It has been repeatedly pointed out that this view is likely to be too extreme [49], [50]. Although it has been shown that many lincRNA genes are evolutionarily conserved and perform various functions [7], [12]–[17], an unknown fraction of lincRNAs should be expected to result from functionally irrelevant background transcription [19]. In the present work, phylogenetic conservation is the principal support of functional relevance of lincRNAs.…”

“…Such transcripts could results from utilization of alternative poly(A) addition signals and/or could represent alternative splice forms separated by long introns [3], [18], [19], [34]. If many purported lincRNAs actually are fragments of protein-coding genes, one would expect a strong correlation to exist between the expression of lincRNAs and neighboring protein-coding genes.…”

“…A popular view that the vast majority of lincRNAs are by-products of background transcription, “simply the noise emitted by a busy machine” [18], [19], is rooted in their typically low abundance and poor evolutionary conservation compared to protein-coding sequences and small RNAs such as miRNAs and snoRNAs [20]. However, some of the lincRNAs do contain strongly conserved regions [21], and most lincRNAs show reduced substitution and insertion/deletion rates suggestive of purifying selection [12], [22], [23].…”

The Persistent Contributions of RNA to Eukaryotic Gen(om)e Architecture and Cellular Function

“…A simple explanation is the increased coverage with ultradeep sequencing methods and coverage of any cell type including tumors, many developmental stages, as well as (tumor) cell lines numerous times over (Carninci 2009;Ritz et al 2011;Haas et al 2012;Ho et al 2012;Shah et al 2012;Eswaran et al 2013;Hu et al 2013;Schonberg et al 2013;Yoshihara et al 2013). With all this overabundance, there is a debate raging between those that claim almost any identified transcript and snippet of RNA to be functional (Mattick 2003;Lee et al 2009;Carninci 2010;Kishore et al 2010;Clark et al 2011;Bernstein et al 2012;Kapranov and St Laurent 2012;Khayrullina et al 2012;Gebetsberger and Polacek 2013;Mattick and Dinger 2013) and more conservative voices (Brosius 2005c;Huttenhofer et al 2005;Robinson 2010;van Bakel et al 2010;Graur et al 2013). The writer concurs with the argumentation for spurious and stochastic transcripts (Kowalczyk et al 2012;Jensen et al 2013;Mudge et al 2013), especially as many transcription promoters are bidirectional (Seila et al 2008;Neil et al 2009;Xu et al 2009;Wei et al 2011;Uesaka et al 2014).…”

Exome RNA sequencing reveals rare and novel alternative transcripts

“…The unprecedented levels of sensitivity and low background of deep RNA-seq compared with other methods (6,7), enable the identification and characterization of previously unannotated gene structures, exons and alternative splice isoforms (8–12). At the same time, the apparent differences between expression array results and RNA-seq data have initiated a discussion regarding the true nature and function of low level pervasive transcription (13,14). To a large extent, these differences may be explained by the fact that arrays are targeting specific subsets of the total pool of RNA, whereas RNA-seq targets all transcripts.…”