Gene and Stem Cell Therapy Program, Centenary Institute, Camperdown 2050, Australia.
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.
内含子保留（IR）是一种广泛公认的剪接错误的结果，导致内含子序列从前信使 RNA 中切除失败。我们对正常白细胞分化的转录组和蛋白质组数据的生物信息学分析揭示了 IR 是基因表达控制的一种生理机制。IR 调节 86 个功能相关基因的表达，包括那些决定粒细胞特有的核形状的基因。特定基因中内含子的保留与剪接因子的下调和 GC 含量的增加有关。IR 在人类和小鼠之间是保守的，通过触发无意义介导的降解（NMD）途径导致 mRNA 和蛋白质水平降低。与 NMD 仅限于编码异常蛋白质的 mRNA 的流行观点相反，我们的数据表明，IR 与 NMD 相结合是正常粒细胞发生中的一种保守机制。生理 IR 可能在持续基因翻译之前提供一种能量上有利的动态基因表达控制水平。
