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/2017/05/10/136275.abstract
AB The human genome encodes an unknown diversity of genes and isoforms. RNA Sequencing (RNA-Seq) suffers from an expression-dependent bias that impedes discovery of low-abundance transcripts and has prevented a complete census of human gene expression. Here 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 and identifies a fundamental distinction in the architecture of protein-coding and noncoding genes. Unlike their coding counterparts, and in contrast to the impression from more shallow surveys, noncoding exons undergo near-universal alternative splicing to produce an effectively inexhaustible variety of isoforms. Targeted RNA-Seq analysis of syntenic regions of the mouse genome indicates that few noncoding exons are shared between human and mouse. Despite this divergence, human alternative splicing profiles are recapitulated on Hsa21 in mouse nuclei, implying regulation by a local splicing code that is more strongly conserved than the noncoding isoforms themselves. We propose that noncoding exons are functionally modular, with combinatorial alternative splicing generating an enormous repertoire of potential regulatory RNAs and a rich transcriptional reservoir for adaptive gene evolution.