Dynamic m(6)A methylation facilitates mRNA triaging to stress granules.
Dynamic m(6)A methylation facilitates mRNA triaging to stress granules.
复制标题
DOI：
10.26508/lsa.201800113
复制
发表时间：
2018-08
影响因子：
4.4
通讯作者：
Ignatova Z
中科院分区：
文献类型：
--
作者：
Anders M;Chelysheva I;Goebel I;Trenkner T;Zhou J;Mao Y;Verzini S;Qian SB;Ignatova Z
转录本编码序列5 '附近的m6A修饰提供了一种将mrna筛选到应激颗粒的选择性机制，并由YTHDF3“阅读器”蛋白介导。信使RNA的可逆转录后修饰是RNA代谢中普遍存在的现象。其中最丰富的是n6 -甲基腺苷（m6A），它是RNA代谢和功能的关键；它在应激反应中的作用仍然难以捉摸。我们发现，在对氧化应激的反应中，转录本在其5 '附近有额外的m6A修饰。与翻译活性mrna不同的是，这种甲基化模式提供了一种选择性机制，可以将mrna从可翻译池中筛选到应激诱导的应激颗粒中。这些胁迫诱导的新甲基化位点被YTH结构域家族3 （YTHDF3）“阅读器”蛋白选择性识别，从而揭示了YTHDF3在形成胁迫反应选择性中的新作用。我们的研究结果描述了RNA m6A修饰在氧化应激反应中的一个以前未被认识到的功能，并扩大了m6A的生理作用的广度。
m6A modification in the 5′ vicinity of the coding sequence of transcripts provides a selective mechanism for triaging mRNAs to stress granules and is mediated by the YTHDF3 “reader” protein. Reversible post-transcriptional modifications on messenger RNA emerge as prevalent phenomena in RNA metabolism. The most abundant among them is N6-methyladenosine (m6A) which is pivotal for RNA metabolism and function; its role in stress response remains elusive. We have discovered that in response to oxidative stress, transcripts are additionally m6A modified in their 5′ vicinity. Distinct from that of the translationally active mRNAs, this methylation pattern provides a selective mechanism for triaging mRNAs from the translatable pool to stress-induced stress granules. These stress-induced newly methylated sites are selectively recognized by the YTH domain family 3 (YTHDF3) “reader” protein, thereby revealing a new role for YTHDF3 in shaping the selectivity of stress response. Our findings describe a previously unappreciated function for RNA m6A modification in oxidative-stress response and expand the breadth of physiological roles of m6A.