TRMT6/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer.
TRMT6/61A-dependent base methylation of tRNA-derived fragments regulates gene-silencing activity and the unfolded protein response in bladder cancer.
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tRNA衍生片段的TRMT 6/61 A依赖性碱基甲基化调节膀胱癌中的基因沉默活性和未折叠蛋白反应
DOI：
10.1038/s41467-022-29790-8
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发表时间：
2022-04-20
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
RNA修饰是RNA功能的重要调控元件。然而，大多数RNA修饰的全基因组映射都集中在信使RNA和转移RNA上，但这样的数据集缺乏小RNA。在这里，我们映射N1-甲基腺苷（m1A）在细胞的小RNA空间。以合成的m1A RNA为基准，我们的工作流程鉴定了含有m1A的小RNA的特定组，这些小RNA在其他方面表现不佳。特别是，22个核苷酸长的3′ tRNA片段高度富集位于种子区域内的TRMT 6/61 A依赖性m1A。TRMT 6/61 A依赖性m1A对tRF-3s的基因沉默产生负面影响。在膀胱尿路上皮癌中，TRMT 6/61 A过表达，检测到tRF上的较高m1A修饰，与tRF targetome的失调相关。最后，TRMT 6/61 A调节参与未折叠蛋白应答的tRF-3靶标。总之，我们的研究结果揭示了通过小RNA的碱基修饰调节基因表达的机制。RNA修饰是RNA生物学的重要调节因子。在这里，我们报告N1-甲基腺苷（m1A）富集22个核苷酸的tRNA片段及其对基因沉默的影响。膀胱癌中较高水平的m1A伴随着未折叠蛋白反应的基因失调。
RNA modifications are important regulatory elements of RNA functions. However, most genome-wide mapping of RNA modifications has focused on messenger RNAs and transfer RNAs, but such datasets have been lacking for small RNAs. Here we mapped N1-methyladenosine (m1A) in the cellular small RNA space. Benchmarked with synthetic m1A RNAs, our workflow identified specific groups of m1A-containing small RNAs, which are otherwise disproportionally under-represented. In particular, 22-nucleotides long 3′ tRNA-fragments are highly enriched for TRMT6/61A-dependent m1A located within the seed region. TRMT6/61A-dependent m1A negatively affects gene silencing by tRF-3s. In urothelial carcinoma of the bladder, where TRMT6/61A is over-expressed, higher m1A modification on tRFs is detected, correlated with a dysregulation of tRF targetome. Lastly, TRMT6/61A regulates tRF-3 targets involved in unfolded protein response. Together, our results reveal a mechanism of regulating gene expression via base modification of small RNA. RNA modifications are important regulators of RNA biology. Here we report N1-methyladenosine (m1A) enrichment on 22-nucleotide tRNA fragments and its effect on gene-silencing. Higher level of m1A in bladder cancer is accompanied by gene dysregulation in unfolded protein response.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
14.9
作者：
Chan PP;Lowe TM
通讯作者：
Lowe TM
影响因子：
5.6
作者：
Finer-Moore J;Czudnochowski N;O'Connell JD 3rd;Wang AL;Stroud RM
通讯作者：
Stroud RM
影响因子：
14.9
作者：
Colaprico A;Silva TC;Olsen C;Garofano L;Cava C;Garolini D;Sabedot TS;Malta TM;Pagnotta SM;Castiglioni I;Ceccarelli M;Bontempi G;Noushmehr H
通讯作者：
Noushmehr H
影响因子：
3.5
作者：
Bruch A;Klassen R;Schaffrath R
通讯作者：
Schaffrath R