N-terminal acetylation is one of the most common protein modifications in eukaryotes, and approximately 40% of human and plant proteomes are acetylated by ribosome-associated N-terminal acetyltransferase A (NatA) in a co-translational manner. However, the in vivo regulatory mechanism of NatA and the global impact of NatA-mediated N-terminal acetylation on protein fate remain unclear. Here, we identify Huntingtin Yeast partner K (HYPK), an evolutionarily conserved chaperone-like protein, as a positive regulator of NatA activity in rice. We found that loss of OsHYPK function leads to developmental defects in rice plant architecture but increased resistance to abiotic stresses, attributable to perturbation of the N-terminal acetylome and accelerated global protein turnover. Furthermore, we demonstrated that OsHYPK is also a substrate of NatA and that N-terminal acetylation of OsHYPK promotes its own degradation, probably through the Ac/N-degron pathway, which could be induced by abiotic stresses. Taken together, our findings suggest that the OsHYPK-NatA complex plays a critical role in coordinating plant development and stress responses by dynamically regulating NatA-mediated N-terminal acetylation and global protein turnover, which are essential for maintaining adaptive phenotypic plasticity in rice.

N-末端乙酰化是真核生物中最常见的蛋白质修饰之一，大约 40% 的人类和植物蛋白质组被核糖体相关的 N-末端乙酰转移酶 A (NatA) 以共翻译方式乙酰化。然而， NatA的体内调控机制以及 NatA 介导的 N 末端乙酰化对蛋白质命运的整体影响仍不清楚。在这里，我们确定亨廷顿酵母伴侣 K (HYPK)，一种进化上保守的伴侣蛋白，作为水稻中 NatA 活性的正调节剂。我们发现OsHYPK的丢失功能导致水稻植株结构发育缺陷，但增加了对非生物胁迫的抵抗力，这归因于 N 末端乙酰组的扰动和加速的全球蛋白质周转。此外，我们证明 OsHYPK 也是 NatA 的底物，并且 OsHYPK 的 N 末端乙酰化促进了其自身的降解，可能通过 Ac/N-degron 途径，这可能是由非生物胁迫诱导的。总之，我们的研究结果表明，OsHYPK-NatA 复合物通过动态调节 NatA 介导的 N 末端乙酰化和整体蛋白质周转在协调植物发育和胁迫响应中发挥关键作用，这对于维持水稻的适应性表型可塑性至关重要。