Cho Hana, Kim Kyoung Mi, Kim Yoon Ki
School of Life Sciences and Biotechnology, Korea University, Seoul 136-701, Republic of Korea.
Mol Cell. 2009 Jan 16;33(1):75-86. doi: 10.1016/j.molcel.2008.11.022.
Nonsense-mediated mRNA decay (NMD) is the best-characterized mRNA surveillance mechanism by which aberrant mRNAs harboring premature termination codons are degraded before translation. However, to date, how NMD machinery recruits the general decay complex to faulty mRNAs and degrades those mRNAs remains unclear. Here we identify human proline-rich nuclear receptor coregulatory protein 2 (PNRC2) as a Upf1- and Dcp1a-interacting protein. Downregulation of PNRC2 abrogates NMD, and artificially tethering PNRC2 downstream of a normal termination codon reduces mRNA abundance. Accordingly, PNRC2 preferentially interacts with hyperphosphorylated Upf1 compared with wild-type Upf1 and triggers movement of hyperphosphorylated Upf1 into processing bodies (P bodies). Our observations suggest that PNRC2 plays an essential role in mammalian NMD, mediating the interaction between the NMD machinery and the decapping complex, so as to target the aberrant mRNA-containing RNPs into P bodies.
无义介导的mRNA降解（NMD）是目前了解最为透彻的mRNA监测机制，通过该机制，携带提前终止密码子的异常mRNA在翻译前就会被降解。然而，迄今为止，NMD机制如何将一般降解复合体招募到有缺陷的mRNA上并降解这些mRNA仍不清楚。在此，我们鉴定出富含脯氨酸的人核受体共调节蛋白2（PNRC2）是一种与Upf1和Dcp1a相互作用的蛋白。PNRC2的下调会消除NMD，而在正常终止密码子下游人工连接PNRC2会降低mRNA丰度。因此，与野生型Upf1相比，PNRC2更倾向于与过度磷酸化的Upf1相互作用，并促使过度磷酸化的Upf1进入加工小体（P小体）。我们的观察结果表明，PNRC2在哺乳动物NMD中起关键作用，介导NMD机制与脱帽复合体之间的相互作用，从而将含有异常mRNA的核糖核蛋白靶向转运到P小体中。
