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
- Publication Type:
- Journal Article
- Citation:
- Cell, 2013, 154 (3), pp. 583 - 595
- Issue Date:
- 2013-08-01
Closed Access
Filename | Description | Size | |||
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1-s2.0-S0092867413008349-main.pdf | Published Version | 3.87 MB | Adobe PDF |
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Full metadata record
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 |
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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