Stem Cell Program, Division of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Ludwig Institute for Cancer Research, University of Oxford, Roosevelt Dr, Headington, Oxford OX3 7DQ, UK.
Mol Cell. 2023 Feb 2;83(3):428-441. doi: 10.1016/j.molcel.2023.01.006.
Since the early days of foundational studies of nucleic acids, many chemical moieties have been discovered to decorate RNA and DNA in diverse organisms. In mammalian cells, one of these chemical modifications, N6-methyl adenosine (m6A), is unique in a way that it is highly abundant not only on RNA polymerase II (RNAPII) transcribed, protein-coding transcripts but also on non-coding RNAs, such as ribosomal RNAs and snRNAs, mediated by distinct, evolutionarily conserved enzymes. Here, we review RNA m6A modification in the light of the recent appreciation of nuclear roles for m6A in regulating chromatin states and gene expression, as well as the recent discoveries of the evolutionarily conserved methyltransferases, which catalyze methylation of adenosine on diverse sets of RNAs. Considering that the substrates of these enzymes are involved in many important biological processes, this modification warrants further research to understand the molecular mechanisms and functions of m6A in health and disease.
自核酸基础研究的早期以来，已经发现许多化学基团可以在不同的生物体中修饰 RNA 和 DNA。在哺乳动物细胞中，这些化学修饰之一，N6-甲基腺苷（m6A），是独特的，它不仅在 RNA 聚合酶 II（RNAPII）转录的、编码蛋白质的转录本上高度丰富，而且在非编码 RNA 上也丰富，如核糖体 RNA 和 snRNA，由不同的、进化上保守的酶介导。在这里，我们根据最近对 m6A 在调节染色质状态和基因表达中的核作用的认识，以及最近发现的进化上保守的甲基转移酶，来综述 RNA m6A 修饰，这些酶催化不同 RNA 上腺苷的甲基化。考虑到这些酶的底物参与许多重要的生物学过程，这种修饰值得进一步研究，以了解 m6A 在健康和疾病中的分子机制和功能。
