Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA; Department of Chemistry and Pharmaceutical Sciences, VU University Amsterdam, De Boelelaan 1083, 1081 HZ Amsterdam, Netherlands.
Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065, USA.
Mol Cell. 2020 May 21;78(4):765-778.e7. doi: 10.1016/j.molcel.2020.03.023. Epub 2020 Apr 15.
Increasing evidence suggests that tRNA levels are dynamically and specifically regulated in response to internal and external cues to modulate the cellular translational program. However, the molecular players and the mechanisms regulating the gene-specific expression of tRNAs are still unknown. Using an inducible auxin-degron system to rapidly deplete RPB1 (the largest subunit of RNA Pol II) in living cells, we identified Pol II as a direct gene-specific regulator of tRNA transcription. Our data suggest that Pol II transcription robustly interferes with Pol III function at specific tRNA genes. This activity was further found to be essential for MAF1-mediated repression of a large set of tRNA genes during serum starvation, indicating that repression of tRNA genes by Pol II is dynamically regulated. Hence, Pol II plays a direct and central role in the gene-specific regulation of tRNA expression.
越来越多的证据表明，tRNA 水平会针对内部和外部信号做出动态且特异性的调节，从而调节细胞的翻译程序。然而，调节 tRNA 基因特异性表达的分子机制仍不清楚。本研究使用诱导型生长素降解系统快速耗尽活细胞中的 RPB1（RNA Pol II 的最大亚基），鉴定出 Pol II 是 tRNA 转录的直接基因特异性调控因子。研究数据表明，Pol II 转录会强烈干扰特定 tRNA 基因处的 Pol III 功能。这一活性对于血清饥饿时 MAF1 介导的大量 tRNA 基因抑制至关重要，表明 Pol II 对 tRNA 基因的抑制是动态调节的。因此，Pol II 在 tRNA 表达的基因特异性调控中发挥直接且核心的作用。
