RT Journal Article
SR Electronic
T1 Universal alternative splicing of noncoding exons
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 136275
DO 10.1101/136275
A1 Ira W. Deveson
A1 Marion E. Brunck
A1 James Blackburn
A1 Elizabeth Tseng
A1 Ting Hon
A1 Tyson A. Clark
A1 Michael B. Clark
A1 Joanna Crawford
A1 Marcel E. Dinger
A1 Lars K. Nielsen
A1 John S. Mattick
A1 Tim R. Mercer
YR 2017
UL http://biorxiv.org/content/early/2017/12/18/136275.abstract
AB The human transcriptome is so large, diverse and dynamic that, even after a decade of investigation by RNA sequencing (RNA-Seq), we are yet to resolve its true dimensions. RNA-Seq suffers from an expression-dependent bias that impedes characterization of low-abundance transcripts. We performed targeted single-molecule and short-read RNA-Seq to survey the transcriptional landscape of a single human chromosome (Hsa21) at unprecedented resolution. Our analysis reaches the lower limits of the transcriptome, identifying a fundamental distinction between protein-coding and noncoding gene content: almost every noncoding exon undergoes alternative splicing, producing a seemingly limitless variety of isoforms. Analysis of syntenic regions of the mouse genome shows that few noncoding exons are shared between human and mouse, yet human splicing profiles are recapitulated on Hsa21 in mouse cells, indicative of regulation by a deeply conserved splicing code. We propose that noncoding exons are functionally modular, with alternative splicing generating an enormous repertoire of potential regulatory RNAs and a rich transcriptional reservoir for gene evolution.