Abstract

Post-transcriptional methylation of N6-adenine and N1-adenine can affect transcriptome turnover and translation. Furthermore, the regulatory function of N6-methyladenine (m⁶A) during heat shock has been uncovered, including the enhancement of the phase separation potential of RNAs. In response to acute stress, e.g. heat shock, the orderly sequestration of mRNAs in stress granules (SGs) is considered important to protect transcripts from the irreversible aggregation. Until recently, the role of N1-methyladenine (m¹A) on mRNAs during acute stress response remains largely unknown. Here we show that the methyltransferase complex TRMT6/61A, which generates the m¹A tag, is involved in transcriptome protection during heat shock. Our bioinformatics analysis indicates that occurrence of the m¹A motif is increased in mRNAs known to be enriched in SGs. Accordingly, the m¹A-generating methyltransferase TRMT6/61A accumulated in SGs and mass spectrometry confirmed enrichment of m¹A in the SG RNAs. The insertion of a single methylation motif in the untranslated region of a reporter RNA leads to more efficient recovery of protein synthesis from that transcript after the return to normal temperature. Our results demonstrate far-reaching functional consequences of a minimal RNA modification on N1-adenine during acute proteostasis stress.

中文翻译：

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m1A 在应激诱导粒化过程中的保护作用

 抽象的

N6-腺嘌呤和 N1-腺嘌呤的转录后甲基化可影响转录组更新和翻译。此外，N6-甲基腺嘌呤（m ⁶ A）在热激过程中的调节功能也已被揭示，包括增强RNA的相分离电位。响应于急性应激，例如热休克，应激颗粒（SG）中mRNA的有序隔离被认为对于保护转录物免于不可逆聚集很重要。直到最近，N1-甲基腺嘌呤 (m ¹ A) 在急性应激反应期间对 mRNA 的作用仍然很大程度上未知。在这里，我们表明，产生 m ¹ A 标签的甲基转移酶复合物 TRMT6/61A 参与热激期间的转录组保护。我们的生物信息学分析表明，m ¹ A 基序的出现在已知富含 SG 的 mRNA 中增加。因此，产生m ¹ A的甲基转移酶TRMT6/61A在SG中积累，并且质谱分析证实了SG RNA中m ¹ A的富集。在报告RNA的非翻译区域插入单个甲基化基序可以在恢复正常温度后更有效地恢复该转录物的蛋白质合成。我们的结果表明，在急性蛋白质稳态应激期间，N1-腺嘌呤上的最小 RNA 修饰会产生深远的功能后果。