DNA damage-induced cell death relies on SLFN11-dependent cleavage of distinct type II tRNAs.
DNA damage-induced cell death relies on SLFN11-dependent cleavage of distinct type II tRNAs.
复制标题
DOI：
10.1038/s41594-018-0142-5
复制
发表时间：
2018-11
影响因子：
16.8
通讯作者：
David M
中科院分区：
文献类型：
--
作者：
Li M;Kao E;Malone D;Gao X;Wang JYJ;David M
Transcriptome analysis revealed a strong positive correlation between human SLFN11 expression and the sensitivity of tumor cells to DNA damaging agents (DDAs). We show here that SLFN11 preferentially inhibits translation of ATR or ATM upon DDAs treatment based on distinct codon usage without disrupting early DNA damage response signaling. Type II tRNAs, which include all serine and leucine tRNAs, are cleaved in a SLFN11-dependent manner in response to DDAs. mRNAs encoded by genes with high TTA (Leu) codon usage such as ATR display utmost susceptibility to translational suppression by SLFN11. Specific attenuation of tRNA-Leu-TAA sufficed to ablate ATR protein expression and restore DDA sensitivity of SLFN11-deficient cells. Our study uncovered a novel mechanism of codon-specific translational inhibition via SLFN11-dependent tRNA cleavage in the DNA damage response, and supports the notion that SLFN11-deficient tumor cells can be resensitized to DDAs by targeting ATR or tRNA-Leu-TAA.
登录
查看更多内容
影响因子：
14.9
作者：
Chan PP;Lowe TM
通讯作者：
Lowe TM
影响因子：
5.5
作者：
Puigbo, Pere;Bravo, Ignacio G.;Garcia-Vallve, Santiago
通讯作者：
Garcia-Vallve, Santiago
Schlafen13 的结构揭示了一类新型 tRNA/rRNA 靶向参与翻译控制的 RNase
影响因子：
16.6
作者：
Yang JY;Deng XY;Li YS;Ma XC;Feng JX;Yu B;Chen Y;Luo YL;Wang X;Chen ML;Fang ZX;Zheng FX;Li YP;Zhong Q;Kang TB;Song LB;Xu RH;Zeng MS;Chen W;Zhang H;Xie W;Gao S
通讯作者：
Gao S
影响因子：
14.9
作者：
Grünweller, A;Wyszko, E;Kurreck, J
通讯作者：
Kurreck, J
影响因子：
7.7
作者：
Mu, Yanhua;Lou, Jiangman;Huang, Jun
通讯作者：
Huang, Jun