Orchestrated intron retention regulates normal granulocyte differentiation

Wong, JJL; Ritchie, W; Ebner, OA; Selbach, M; Wong, JWH; Huang, Y; Gao, D; Pinello, N; Gonzalez, M; Baidya, K; Thoeng, A; Khoo, TL; Bailey, CG; Holst, J; Rasko, JEJ

Orchestrated intron retention regulates normal granulocyte differentiation

Wong, JJL Ritchie, W Ebner, OA Selbach, M Wong, JWH Huang, Y

Gao, D Pinello, N Gonzalez, M Baidya, K Thoeng, A Khoo, TL Bailey, CG Holst, J Rasko, JEJ

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Publication Type:: Journal Article
Citation:: Cell, 2013, 154 (3), pp. 583 - 595
Issue Date:: 2013-08-01

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Field	Value	Language
dc.contributor.author	Wong, JJL	en_US
dc.contributor.author	Ritchie, W	en_US
dc.contributor.author	Ebner, OA	en_US
dc.contributor.author	Selbach, M	en_US
dc.contributor.author	Wong, JWH	en_US
dc.contributor.author	Huang, Y https://orcid.org/0000-0002-7003-3110	en_US
dc.contributor.author	Gao, D	en_US
dc.contributor.author	Pinello, N	en_US
dc.contributor.author	Gonzalez, M	en_US
dc.contributor.author	Baidya, K	en_US
dc.contributor.author	Thoeng, A	en_US
dc.contributor.author	Khoo, TL	en_US
dc.contributor.author	Bailey, CG	en_US
dc.contributor.author	Holst, J	en_US
dc.contributor.author	Rasko, JEJ	en_US
dc.date.available	2013-06-28	en_US
dc.date.issued	2013-08-01	en_US
dc.identifier.citation	Cell, 2013, 154 (3), pp. 583 - 595	en_US
dc.identifier.issn	0092-8674	en_US
dc.identifier.uri	http://hdl.handle.net/10453/132443
dc.description.abstract	Intron retention (IR) is widely recognized as a consequence of mis-splicing that leads to failed excision of intronic sequences from pre-messenger RNAs. Our bioinformatic analyses of transcriptomic and proteomic data of normal white blood cell differentiation reveal IR as a physiological mechanism of gene expression control. IR regulates the expression of 86 functionally related genes, including those that determine the nuclear shape that is unique to granulocytes. Retention of introns in specific genes is associated with downregulation of splicing factors and higher GC content. IR, conserved between human and mouse, led to reduced mRNA and protein levels by triggering the nonsense-mediated decay (NMD) pathway. In contrast to the prevalent view that NMD is limited to mRNAs encoding aberrant proteins, our data establish that IR coupled with NMD is a conserved mechanism in normal granulopoiesis. Physiological IR may provide an energetically favorable level of dynamic gene expression control prior to sustained gene translation. © 2013 Elsevier Inc.	en_US
dc.relation.ispartof	Cell	en_US
dc.relation.isbasedon	10.1016/j.cell.2013.06.052	en_US
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject.classification	Developmental Biology	en_US
dc.subject.mesh	Granulocytes	en_US
dc.subject.mesh	Cell Nucleus	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred C57BL	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Lamin Type B	en_US
dc.subject.mesh	Hematopoiesis	en_US
dc.subject.mesh	Down-Regulation	en_US
dc.subject.mesh	RNA Splicing	en_US
dc.subject.mesh	Base Composition	en_US
dc.subject.mesh	Introns	en_US
dc.subject.mesh	Algorithms	en_US
dc.subject.mesh	Nonsense Mediated mRNA Decay	en_US
dc.title	Orchestrated intron retention regulates normal granulocyte differentiation	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	154	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
utslib.copyright.status	closed_access	*
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	154	en_US

Abstract:

Intron retention (IR) is widely recognized as a consequence of mis-splicing that leads to failed excision of intronic sequences from pre-messenger RNAs. Our bioinformatic analyses of transcriptomic and proteomic data of normal white blood cell differentiation reveal IR as a physiological mechanism of gene expression control. IR regulates the expression of 86 functionally related genes, including those that determine the nuclear shape that is unique to granulocytes. Retention of introns in specific genes is associated with downregulation of splicing factors and higher GC content. IR, conserved between human and mouse, led to reduced mRNA and protein levels by triggering the nonsense-mediated decay (NMD) pathway. In contrast to the prevalent view that NMD is limited to mRNAs encoding aberrant proteins, our data establish that IR coupled with NMD is a conserved mechanism in normal granulopoiesis. Physiological IR may provide an energetically favorable level of dynamic gene expression control prior to sustained gene translation. © 2013 Elsevier Inc.

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http://hdl.handle.net/10453/132443