Role of SMG ‐1‐mediated U pf1 phosphorylation in mammalian nonsense‐mediated m RNA decay

SMG ‐1, a member of the PIKK (phosphoinositide 3‐kinase‐related kinase) family, plays a critical role in the m RNA quality control system known as nonsense‐mediated m RNA decay ( NMD ). NMD protects cells from the accumulation of aberrant m RNA s with premature termination codons ( PTC s) which encode nonfunctional or potentially harmful truncated proteins. SMG ‐1 directly phosphorylates U pf1 helicase, another key component of NMD , upon recognition of PTC on postspliced m RNA during the initial round of translation. Phosphorylated‐ U pf1 recruits the SMG ‐5/ SMG ‐7 complex to induce ribosome dissociation and decapping‐mediated decay. Phospho‐ U pf1 also recruits the SMG ‐6 endonuclease which might be involved in endo‐cleavage. U pf1 ATP ase/helicase activities are likely required for the activation of other m RNA decay enzymes and the m RNA ‐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.