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

Research output: Contribution to journalJournal articleResearchpeer-review

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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., ... 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
Deveson, Ira W ; Brunck, Marion E ; Blackburn, James ; Tseng, Elizabeth ; Hon, Ting ; Clark, Tyson A ; Clark, Michael B ; Crawford, Joanna ; Dinger, Marcel E ; Nielsen, Lars K ; Mattick, John S ; Mercer, Tim R. / Universal Alternative Splicing of Noncoding Exons. In: Cell Systems. 2018 ; Vol. 6, No. 2. pp. 153-155.
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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.",
keywords = "RNA CaptureSeq, RNA sequencing, Alternative splicing, lncRNA, Mammalian transcriptome, Noncoding RNA",
author = "Deveson, {Ira W} and Brunck, {Marion E} and James Blackburn and Elizabeth Tseng and Ting Hon and Clark, {Tyson A} and Clark, {Michael B} and Joanna Crawford and Dinger, {Marcel E} and Nielsen, {Lars K} and Mattick, {John S} and Mercer, {Tim R}",
year = "2018",
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Deveson, IW, Brunck, ME, Blackburn, J, Tseng, E, Hon, T, Clark, TA, Clark, MB, Crawford, J, Dinger, ME, Nielsen, LK, Mattick, JS & Mercer, TR 2018, 'Universal Alternative Splicing of Noncoding Exons', Cell Systems, vol. 6, no. 2, pp. 153-155. https://doi.org/10.1016/j.cels.2017.12.005

Universal Alternative Splicing of Noncoding Exons. / Deveson, Ira W; Brunck, Marion E; Blackburn, James; Tseng, Elizabeth; Hon, Ting; Clark, Tyson A; Clark, Michael B; Crawford, Joanna; Dinger, Marcel E; Nielsen, Lars K; Mattick, John S; Mercer, Tim R.

In: Cell Systems, Vol. 6, No. 2, 2018, p. 153-155.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Universal Alternative Splicing of Noncoding Exons

AU - Deveson, Ira W

AU - Brunck, Marion E

AU - Blackburn, James

AU - Tseng, Elizabeth

AU - Hon, Ting

AU - Clark, Tyson A

AU - Clark, Michael B

AU - Crawford, Joanna

AU - Dinger, Marcel E

AU - Nielsen, Lars K

AU - Mattick, John S

AU - Mercer, Tim R

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - RNA CaptureSeq

KW - RNA sequencing

KW - Alternative splicing

KW - lncRNA

KW - Mammalian transcriptome

KW - Noncoding RNA

U2 - 10.1016/j.cels.2017.12.005

DO - 10.1016/j.cels.2017.12.005

M3 - Journal article

VL - 6

SP - 153

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JF - Cell Systems

SN - 2405-4712

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ER -

Deveson IW, Brunck ME, Blackburn J, Tseng E, Hon T, Clark TA et al. Universal Alternative Splicing of Noncoding Exons. Cell Systems. 2018;6(2):153-155. https://doi.org/10.1016/j.cels.2017.12.005