Orchestrated intron retention regulates normal granulocyte differentiation

Cell. 2013 Aug 1;154(3):583-95. doi: 10.1016/j.cell.2013.06.052.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Base Composition
  • Cell Nucleus / metabolism
  • Down-Regulation
  • Granulocytes / cytology
  • Granulocytes / metabolism*
  • Hematopoiesis*
  • Humans
  • Introns
  • Lamin Type B / genetics
  • Mice
  • Mice, Inbred C57BL
  • Nonsense Mediated mRNA Decay
  • RNA Splicing*


  • Lamin Type B
  • lamin B1

Associated data

  • GEO/GSE48307