Universal Alternative Splicing of Noncoding Exons

Ira W Deveson, Marion E Brunck, James Blackburn, Elizabeth Tseng, Ting Hon, Tyson A Clark, Michael B Clark, Joanna Crawford, Marcel E Dinger, Lars K Nielsen, John S Mattick, Tim R Mercer*

*Corresponding author for this work

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Abstract

The human transcriptome is so large, diverse, and dynamic that, even after a decade of investigation by RNA sequencing (RNA-seq), we have 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.
Original languageEnglish
JournalCell Systems
Volume6
Issue number2
Pages (from-to)153-155
ISSN2405-4712
DOIs
Publication statusPublished - 2018

Keywords

  • RNA CaptureSeq
  • RNA sequencing
  • Alternative splicing
  • lncRNA
  • Mammalian transcriptome
  • Noncoding RNA

Cite this

Deveson, I. W., Brunck, M. E., Blackburn, J., Tseng, E., Hon, T., Clark, T. A., Clark, M. B., Crawford, J., Dinger, M. E., Nielsen, L. K., Mattick, J. S., & Mercer, T. R. (2018). Universal Alternative Splicing of Noncoding Exons. Cell Systems, 6(2), 153-155. https://doi.org/10.1016/j.cels.2017.12.005