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DOI | 10.1038/ncomms15875 |
N-6-methyladenosine mRNA marking promotes selective translation of regulons required for human erythropoiesis | |
Kuppers, Daniel A.1; Arora, Sonali1; Lim, Yiting1; Lim, Andrea R.1,2; Carter, Lucas M.1; Corrin, Philip D.1; Plaisier, Christopher L.3; Basom, Ryan4; Delrow, Jeffrey J.4; Wang, Shiyan5; He, Housheng Hansen5; Torok-Storb, Beverly6; Hsieh, Andrew C.1,6; Paddison, Patrick J.1,7 | |
2019-10-10 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Canada |
英文摘要 | Many of the regulatory features governing erythrocyte specification, maturation, and associated disorders remain enigmatic. To identify new regulators of erythropoiesis, we utilize a functional genomic screen for genes affecting expression of the erythroid marker CD235a/GYPA. Among validating hits are genes coding for the N-6-methyladenosine (m(6)A) mRNA methyltransferase (MTase) complex, including, METTL14, METTL3, and WTAP. We demonstrate that m(6)A MTase activity promotes erythroid gene expression programs through selective translation of similar to 300 m(6)A marked mRNAs, including those coding for SETD histone methyltransferases, ribosomal components, and polyA RNA binding proteins. Remarkably, loss of m(6)A marks results in dramatic loss of H3K4me3 marks across key erythroid-specific KLF1 transcriptional targets (e.g., Heme biosynthesis genes). Further, each m(6)A MTase subunit and a subset of their mRNAs targets are required for human erythroid specification in primary bone-marrow derived progenitors. Thus, m(6)A mRNA marks promote the translation of a network of genes required for human erythropoiesis. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000489557400001 |
WOS关键词 | CXXC FINGER PROTEIN-1 ; METHYLTRANSFERASE COMPLEX ; ERYTHROID-CELLS ; ENRICHMENT ANALYSIS ; EXPRESSION ANALYSIS ; HEMATOPOIETIC STEM ; TUMOR-SUPPRESSOR ; GENE-REGULATION ; GLYCOPHORIN-A ; M(6)A |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203353 |
专题 | 资源环境科学 |
作者单位 | 1.Fred Hutchinson Canc Res Ctr, Human Biol Div, Seattle, WA 98109 USA; 2.Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA; 3.Arizona State Univ, Sch Biol & Hlth Syst Engn, Tempe, AZ 85281 USA; 4.Fred Hutchinson Canc Res Ctr, Genom Shared Resource, Seattle, WA 98109 USA; 5.Univ Hlth Network, Princess Margaret Canc Ctr, Toronto, ON, Canada; 6.Fred Hutchinson Canc Res Ctr, Clin Res Div, Seattle, WA 98109 USA; 7.Univ Washington, Sch Med, Seattle, WA 98195 USA |
推荐引用方式 GB/T 7714 | Kuppers, Daniel A.,Arora, Sonali,Lim, Yiting,et al. N-6-methyladenosine mRNA marking promotes selective translation of regulons required for human erythropoiesis[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Kuppers, Daniel A..,Arora, Sonali.,Lim, Yiting.,Lim, Andrea R..,Carter, Lucas M..,...&Paddison, Patrick J..(2019).N-6-methyladenosine mRNA marking promotes selective translation of regulons required for human erythropoiesis.NATURE COMMUNICATIONS,10. |
MLA | Kuppers, Daniel A.,et al."N-6-methyladenosine mRNA marking promotes selective translation of regulons required for human erythropoiesis".NATURE COMMUNICATIONS 10(2019). |
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