期刊
GENOME RESEARCH
卷 31, 期 8, 页码 1395-1408出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.271635.120
关键词
-
资金
- Wellcome Trust [215513, FC001110]
- Cancer Research UK [FC001110]
- UK Medical Research Council [FC001110]
The m(6)A modification in RNA plays crucial roles in RNA regulation, potentially influencing RNA splicing. The presence of m(6)A peaks in RNA is related to RNA binding sites and histone modifications, and depletion of METTL3 can disrupt RNA splicing, particularly at 5' splice sites. m(6)A can regulate the inclusion of alternative introns/exons and affect the splicing process.
RNA N-6-methyladenosine (m(6)A) modification plays important roles in multiple aspects of RNA regulation. m(6)A is installed cotranscriptionally by the METTL3/14 complex, but its direct roles in RNA processing remain unclear. Here, we investigate the presence of m(6)A in nascent RNA of mouse embryonic stem cells. We find that around 10% of m(6)A peaks are located in alternative introns/exons, often close to 5' splice sites. m(6)A peaks significantly overlap with RBM15 RNA binding sites and the histone modification H3K36me3. Acute depletion of METTL3 disrupts inclusion of alternative introns/exons in the nascent transcriptome, particularly at 5' splice sites that are proximal to m(6)A peaks. For terminal or variable-length exons, m(6)A peaks are generally located on or immediately downstream from a 5' splice site that is suppressed in the presence of m(6)A and upstream of a 5' splice site that is promoted in the presence of m(6)A. Genes with the most immediate effects on splicing include several components of the m(6)A pathway, suggesting an autoregulatory function. Collectively, our findings demonstrate crosstalk between the m(6)A machinery and the regulation of RNA splicing.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据