GSTDTAP  > 资源环境科学
DOI10.1038/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
ISSN2041-1723
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
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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
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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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