| Abstract: | SMG‐1, a member of the PIKK (phosphoinositide 3‐kinase‐related kinase) family, plays a critical role in the mRNA quality control system known as nonsense‐mediated mRNA decay (NMD). NMD protects cells from the accumulation of aberrant mRNAs with premature termination codons (PTCs) which encode nonfunctional or potentially harmful truncated proteins. SMG‐1 directly phosphorylates Upf1 helicase, another key component of NMD, upon recognition of PTC on postspliced mRNA during the initial round of translation. Phosphorylated‐Upf1 recruits the SMG‐5/SMG‐7 complex to induce ribosome dissociation and decapping‐mediated decay. Phospho‐Upf1 also recruits the SMG‐6 endonuclease which might be involved in endo‐cleavage. Upf1 ATPase/helicase activities are likely required for the activation of other mRNA decay enzymes and the mRNA‐protein complex dissociation to complete NMD. At present, a variety of tools are available that can specifically suppress NMD, and it has become possible to examine the contribution of NMD in a variety of physiological and pathological conditions. |
