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Orchestrated intron retention regulates normal granulocyte differentiation

Item Type:Article
Title:Orchestrated intron retention regulates normal granulocyte differentiation
Creators Name:Wong, J.J.L. and Ritchie, W. and Ebner, O.A. and Selbach, M. and Wong, J.W.H. and Huang, Y. and Gao, D. and Pinello, N. and Gonzalez, M. and Baidya, K. and Thoeng, A. and Khoo, T.L. and Bailey, C.G. and Holst, J. and Rasko, J.E.J.
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.
Keywords:Algorithms, Base Composition, Cell Nucleus, Down-Regulation, Granulocytes, Hematopoiesis, Introns, Lamin Type B, Nonsense Mediated mRNA Decay, RNA Splicing, Animals, Mice
Publisher:Cell Press
Page Range:583-595
Date:1 August 2013
Official Publication:https://doi.org/10.1016/j.cell.2013.06.052
PubMed:View item in PubMed

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