北京大学Ying Liu团队近期取得重要工作进展，他们通过全基因组CRISPR筛选确定ILF3是mTORC1依赖性氨基酸传感的介质。相关研究成果2023年4月10日在线发表于《自然—细胞生物学》杂志上。

据介绍，雷帕霉素复合物1（mTORC1）的机制靶标是整合营养信号和协调代谢以控制细胞生长的重要枢纽。氨基酸信号由传感器蛋白检测，并传递到GATOR2和GATOR1复合物以控制mTORC1活性。

研究人员进行全基因组CRISPR/Cas9筛选，结合基于pS6的荧光激活细胞分选分析的mTORC1活性测定，以确定mTORC1依赖性氨基酸传感的潜在调节因子。研究人员将重点放在白细胞介素增强子结合因子3（ILF3）上，这是来自筛选的候选基因之一。ILF3将GATOR复合物与溶酶体连接以控制mTORC1。将溶酶体靶向序列添加到GATOR2组分WDR24中，绕过了对ILF3调节氨基酸依赖性mTORC1信号传导的要求。

总之，这一发现表明，ILF3在人类和小鼠细胞以及蠕虫中发挥演化保守的作用，调节mTORC1通路，控制自噬活性并调节衰老过程。

附：英文原文

Title: Genome-wide CRISPR screens identify ILF3 as a mediator of mTORC1-dependent amino acid sensing

Author: Yan, Guokai, Yang, Jinxin, Li, Wen, Guo, Ao, Guan, Jialiang, Liu, Ying

Issue&Volume: 2023-04-10

Abstract: The mechanistic target of rapamycin complex 1 (mTORC1) is an essential hub that integrates nutrient signals and coordinates metabolism to control cell growth. Amino acid signals are detected by sensor proteins and relayed to the GATOR2 and GATOR1 complexes to control mTORC1 activity. Here we perform genome-wide CRISPR/Cas9 screens, coupled with an assay for mTORC1 activity based on fluorescence-activated cell sorting analysis of pS6, to identify potential regulators of mTORC1-dependent amino acid sensing. We then focus on interleukin enhancer binding factor 3 (ILF3), one of the candidate genes from the screen. ILF3 tethers the GATOR complexes to lysosomes to control mTORC1. Adding a lysosome-targeting sequence to the GATOR2 component WDR24 bypasses the requirement for ILF3 to modulate amino-acid-dependent mTORC1 signalling. ILF3 plays an evolutionarily conserved role in human and mouse cells, and in worms to regulate the mTORC1 pathway, control autophagy activity and modulate the ageing process.

DOI: 10.1038/s41556-023-01123-x

Source: https://www.nature.com/articles/s41556-023-01123-x