Encinar Del Dedo Javier, Suárez M Belén, López-San Segundo Rafael, Vázquez-Bolado Alicia, Sun Jingjing, García-Blanco Natalia, García Patricia, Tricquet Pauline, Chen Jun-Song, Dedon Peter C, Gould Kathleen L, Hidalgo Elena, Hermand Damien, Moreno Sergio
Instituto de Biología Funcional y Genómica, CSIC, University of Salamanca, 37007, Salamanca, Spain.
Instituto de Biología Funcional y Genómica, University of Salamanca, CSIC, 37007, Salamanca, Spain.
Nat Commun. 2024 Dec 5;15(1):10603. doi: 10.1038/s41467-024-55004-4.
Quiescent cells require a continuous supply of proteins to maintain protein homeostasis. In fission yeast, entry into quiescence is triggered by nitrogen stress, leading to the inactivation of TORC1 and the activation of TORC2. In this study, we demonstrate that the Greatwall-Endosulfine-PPA/B55 pathway connects the downregulation of TORC1 with the upregulation of TORC2, resulting in the activation of Elongator-dependent tRNA modifications crucial for sustaining the translation programme during entry into quiescence. This mechanism promotes U and A tRNA modifications at the anticodon stem loop, enhancing translation efficiency and fidelity of mRNAs enriched for AAA versus AAG lysine codons. Notably, several of these mRNAs encode TORC1 inhibitors, TORC2 activators, tRNA modifiers, and proteins necessary for telomeric and subtelomeric functions. Therefore, we propose a mechanism by which cells respond to nitrogen stress at the level of translation, involving a coordinated interplay between tRNA epitranscriptome and biased codon usage.
静止细胞需要持续供应蛋白质以维持蛋白质稳态。在裂殖酵母中，氮胁迫会触发细胞进入静止状态，导致TORC1失活和TORC2激活。在本研究中，我们证明了Greatwall-Endosulfine-PPA/B55途径将TORC1的下调与TORC2的上调联系起来，从而激活了依赖延伸因子的tRNA修饰，这对于在进入静止状态期间维持翻译程序至关重要。这种机制促进了反密码子茎环处的U和A tRNA修饰，提高了富含AAA与AAG赖氨酸密码子的mRNA的翻译效率和保真度。值得注意的是，这些mRNA中有几种编码TORC1抑制剂、TORC2激活剂、tRNA修饰剂以及端粒和亚端粒功能所需的蛋白质。因此，我们提出了一种细胞在翻译水平上对氮胁迫作出反应的机制，该机制涉及tRNA表观转录组和偏向密码子使用之间的协调相互作用。
