Cellular growth and organismal development are remarkably complex processes that require the nutrient-responsive kinase mechanistic target of rapamycin complex 1 (mTORC1). Anticipating that important mTORC1 functions remained to be identified, we employed genetic and bioinformatic screening in C. elegans to uncover mechanisms of mTORC1 action. Here, we show that during larval growth, nutrients induce an extensive reprogramming of gene expression and alternative mRNA splicing by acting through mTORC1. mTORC1 regulates mRNA splicing and the production of protein-coding mRNA isoforms largely independently of its target p70 S6 kinase (S6K) by increasing the activity of the serine/arginine-rich (SR) protein RSP-6 (SRSF3/7) and other splicing factors. mTORC1-mediated mRNA splicing regulation is critical for growth; mediates nutrient control of mechanisms that include energy, nucleotide, amino acid, and other metabolic pathways; and may be conserved in humans. Although mTORC1 inhibition delays aging, mTORC1-induced mRNA splicing promotes longevity, suggesting that when mTORC1 is inhibited, enhancement of this splicing might provide additional anti-aging benefits.

中文翻译：

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通过 mTORC1 调节 mRNA 剪接对生长和代谢进行营养控制


细胞生长和生物体发育是非常复杂的过程，需要雷帕霉素复合物 1 （mTORC1） 的营养反应性激酶机制靶标。预计重要的 mTORC1 功能仍有待确定，我们在秀丽隐杆线虫中 采用遗传和生物信息学筛选来揭示 mTORC1 作用的机制。在这里，我们表明，在幼虫生长过程中，营养物质通过 mTORC1 作用诱导基因表达和选择性 mRNA 剪接的广泛重编程。mTORC1 通过增加富含丝氨酸/精氨酸 （SR） 的蛋白 RSP-6 （SRSF3/7） 和其他剪接因子的活性，在很大程度上独立于其靶标 p70 S6 激酶 （S6K） 调节 mRNA 剪接和蛋白质编码 mRNA 亚型的产生。mTORC1 介导的 mRNA 剪接调节对生长至关重要;介导包括能量、核苷酸、氨基酸和其他代谢途径在内的机制的营养控制;并且在人类中可能是保守的。尽管 mTORC1 抑制会延缓衰老，但 mTORC1 诱导的 mRNA 剪接可延长寿命，这表明当 mTORC1 受到抑制时，这种剪接的增强可能会提供额外的抗衰老益处。