The cap epitranscriptome: Early directions to a complex life as mRNA
The cap epitranscriptome: Early directions to a complex life as mRNA
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DOI：
10.1002/bies.202200198
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发表时间：
2022-12-18
期刊：
影响因子：
4
通讯作者：
Soller, Matthias
中科院分区：
文献类型：
--
作者：
Anreiter, Ina;Tian, Yuan W.;Soller, Matthias
动物、原生动物和病毒信使RNA(MRNAs)在一开始最显著的修饰是核糖(Come)2‘-O-位上的帽相邻核苷酸的甲基化。如果mRNA的第一个核苷酸是腺苷，PCIF1可以在N-6位(m(6)A)甲基化，而在内部METTL3/14编写器复合体可以甲基化。这些修饰是以共转录的方式引入的，以影响基因表达的许多方面，包括突触的定位和局部翻译。特别值得注意的是，许多基因的转录起始点是异质性的，这导致了mRNAs开始时的序列多样性，与Come和m(6)Am一起构成了一个广泛的新的基因表达调控层。鉴于Come和m(6)A在突触局部基因表达以及包括学习和记忆在内的高级大脑功能中的作用，这种编码可以通过突触局部基因表达在转录水平上实现持久记忆。
Animal, protist and viral messenger RNAs (mRNAs) are most prominently modified at the beginning by methylation of cap-adjacent nucleotides at the 2 ' -O-position of the ribose (cOMe) by dedicated cap methyltransferases (CMTrs). If the first nucleotide of an mRNA is an adenosine, PCIF1 can methylate at the N-6-position (m(6)A), while internally the Mettl3/14 writer complex can methylate. These modifications are introduced co-transcriptionally to affect many aspects of gene expression including localisation to synapses and local translation. Of particular interest, transcription start sites of many genes are heterogeneous leading to sequence diversity at the beginning of mRNAs, which together with cOMe and m(6)Am could constitute an extensive novel layer of gene expression control. Given the role of cOMe and m(6)A in local gene expression at synapses and higher brain functions including learning and memory, such code could be implemented at the transcriptional level for lasting memories through local gene expression at synapses.