CMTr mediated 2'-O-ribose methylation status of cap-adjacent nucleotides across animals.

CMTr mediated 2'-O-ribose methylation status of cap-adjacent nucleotides across animals.
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DOI:
10.1261/rna.079317.122
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发表时间:
2022-10
期刊:
RNA (New York, N.Y.)
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帽甲基转移酶(CMTrs)O甲基化动物、原生生物和病毒mRNA的帽相邻核苷酸的核糖(cOMe)的2′位置。动物通常有两个CMTR,而锥虫有三个,许多病毒在其基因组中编码一个。在锥虫mRNA的剪接前导序列中,前四个核苷酸含有cOMe,但对cOMe在动物中的状态知之甚少。在这里,我们表明,cOMe是显着存在于前两个帽相邻的核苷酸与物种和组织特异性的变化,在秀丽隐杆线虫,蜜蜂,斑马鱼,小鼠和人类细胞系。相比之下,果蝇主要在第一个帽相邻核苷酸上含有cOMe。CMTrs的从头RoseTTA建模揭示了人、果蝇和C.秀丽隐杆线虫尽管病毒CMTR保持了整体结构和催化四分体,但它们在帽和辅因子结合方面有所不同。与结构相似性一致,来自果蝇和人类的CMTR都甲基化AGU共有序列起始的第一个帽相邻核苷酸。由于第二个核苷酸也甲基化后,在果蝇的热应激,这些研究结果表明,调节cOMe基因表达调控的重要性。
Cap methyltransferases (CMTrs) O methylate the 2′ position of the ribose (cOMe) of cap-adjacent nucleotides of animal, protist, and viral mRNAs. Animals generally have two CMTrs, whereas trypanosomes have three, and many viruses encode one in their genome. In the splice leader of mRNAs in trypanosomes, the first four nucleotides contain cOMe, but little is known about the status of cOMe in animals. Here, we show that cOMe is prominently present on the first two cap-adjacent nucleotides with species- and tissue-specific variations in Caenorhabditis elegans, honeybees, zebrafish, mouse, and human cell lines. In contrast, Drosophila contains cOMe primarily on the first cap-adjacent nucleotide. De novo RoseTTA modeling of CMTrs reveals close similarities of the overall structure and near identity for the catalytic tetrad, and for cap and cofactor binding for human, Drosophila and C. elegans CMTrs. Although viral CMTrs maintain the overall structure and catalytic tetrad, they have diverged in cap and cofactor binding. Consistent with the structural similarity, both CMTrs from Drosophila and humans methylate the first cap-adjacent nucleotide of an AGU consensus start. Because the second nucleotide is also methylated upon heat stress in Drosophila, these findings argue for regulated cOMe important for gene expression regulation.
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