Pre-mRNA processing includes N(6) methylation of adenosine residues that are retained in mRNA exons and the fallacy of "RNA epigenetics".
Pre-mRNA processing includes N(6) methylation of adenosine residues that are retained in mRNA exons and the fallacy of "RNA epigenetics".
复制标题
DOI：
10.1261/rna.065219.117
复制
发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Darnell JE Jr
中科院分区：
文献类型：
--
作者：
Darnell RB;Ke S;Darnell JE Jr
通过使用细胞分割技术分离染色质相关的新生RNA、新完成的核质mRNA和细胞质mRNA，我们在先前的研究中发现，外显子的残基在新生的Pre-mRNA中发生甲基化(M6A)，并在核质和细胞质mRNA中保持在相同的外显子残基中甲基化。因此，没有证据表明mR NA外显子有相当程度的去甲基化，这与所谓的“表观遗传”去甲基化相对应。根据HeLa细胞中m6A含量的不同，mR-NA分子的周转速度更快，提示m6A外显子修饰可能是mR-NA稳定性规范的主要作用。在缺乏METTL3(主要的信使核糖核酸甲基酶)的小鼠胚胎干细胞(MESCs)中，细胞继续生长，在信使核糖核酸中没有m6A(90%)的情况下，产生相同的剪接轮廓不变的mRNAs，这表明m6A在剪接中没有共同的强制性作用。所有这些数据都强烈反对普遍使用的“可逆的动态甲基化/去甲基化”的信使核糖核酸表观遗传学的概念受到质疑，该概念与动态DNA表观遗传学的公认作用相平行。
By using a cell fraction technique that separates chromatin-associated nascent RNA, newly completed nucleoplasmic mRNA and cytoplasmic mRNA, we have shown in a previous study that residues in exons are methylated (m6A) in nascent pre-mRNA and remain methylated in the same exonic residues in nucleoplasmic and cytoplasmic mRNA. Thus, there is no evidence of a substantial degree of demethylation in mRNA exons that would correspond to so-called “epigenetic” demethylation. The turnover rate of mRNA molecules is faster, depending on m6A content in HeLa cell mRNA, suggesting that specification of mRNA stability may be the major role of m6A exon modification. In mouse embryonic stem cells (mESCs) lacking Mettl3, the major mRNA methylase, the cells continue to grow, making the same mRNAs with unchanged splicing profiles in the absence (>90%) of m6A in mRNA, suggesting no common obligatory role of m6A in splicing. All these data argue strongly against a commonly used “reversible dynamic methylation/demethylation” of mRNA, calling into question the concept of “RNA epigenetics” that parallels the well-established role of dynamic DNA epigenetics.
登录
查看更多内容
DOI：
10.1073/pnas.72.1.362
发表时间：
1975-01-01
影响因子：
11.1
作者：
FURUICHI, Y;MORGAN, M;SHATKIN, AJ
通讯作者：
SHATKIN, AJ
DOI：
10.1126/science.aad8711
发表时间：
2016-06-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gilbert WV;Bell TA;Schaening C
通讯作者：
Schaening C
影响因子：
64.5
作者：
Bhatt DM;Pandya-Jones A;Tong AJ;Barozzi I;Lissner MM;Natoli G;Black DL;Smale ST
通讯作者：
Smale ST
影响因子：
10.5
作者：
Ke S;Alemu EA;Mertens C;Gantman EC;Fak JJ;Mele A;Haripal B;Zucker-Scharff I;Moore MJ;Park CY;Vågbø CB;Kusśnierczyk A;Klungland A;Darnell JE Jr;Darnell RB
通讯作者：
Darnell RB
影响因子：
64.5
作者：
Meyer KD;Saletore Y;Zumbo P;Elemento O;Mason CE;Jaffrey SR
通讯作者：
Jaffrey SR