MOE Key laboratory of Bioinformatics, Cell Biology and Development Center, School of Life Sciences, Tsinghua University, Beijing, China.
State Key laboratory for Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Fujian, China.
EMBO Rep. 2020 Dec 3;21(12):e49684. doi: 10.15252/embr.201949684. Epub 2020 Oct 19.
mascRNA is a small cytoplasmic RNA derived from the lncRNA MALAT1. After being processed by the tRNA processing enzymes RNase P and RNase Z, mascRNA undergoes CCA addition like tRNAs and folds into a tRNA-like cloverleaf structure. While MALAT1 functions in multiple cellular processes, the role of mascRNA was largely unknown. Here, we show that mascRNA binds directly to the multi-tRNA synthetase complex (MSC) component glutaminyl-tRNA synthetase (QARS). mascRNA promotes global protein translation and cell proliferation by positively regulating QARS protein levels. Our results uncover a role of mascRNA that is independent of MALAT1, but could be part of the molecular mechanism of MALAT1's function in cancer, and provide a paradigm for understanding tRNA-like structures in mammalian cells.
mascRNA 是一种从小核仁 RNA(lncRNA MALAT1)衍生而来的细胞质小分子 RNA。在 tRNA 加工酶 RNase P 和 RNase Z 的加工后,mascRNA 像 tRNA 一样经历 CCA 添加,并折叠成类似 tRNA 的三叶草结构。虽然 MALAT1 在多种细胞过程中发挥作用,但 mascRNA 的作用在很大程度上尚不清楚。在这里,我们表明 mascRNA 直接结合到多功能 tRNA 合成酶复合物(MSC)成分谷氨酰-tRNA 合成酶(QARS)。mascRNA 通过正向调节 QARS 蛋白水平来促进全局蛋白质翻译和细胞增殖。我们的研究结果揭示了 mascRNA 的一个独立于 MALAT1 的作用,但可能是 MALAT1 在癌症中功能的分子机制的一部分,并为理解哺乳动物细胞中类似 tRNA 的结构提供了范例。