Multiple links between 5-methylcytosine content of mRNA and translation

doi:10.1186/s12915-020-00769-5

	Multiple links between 5-methylcytosine content of mRNA and translation
	Schumann, Ulrike 1; Zhang, He-Na 2; Sibbritt, Tennille 1; Pan, Anyu 1; Horvath, Attila 1; Gross, Simon 1; Clark, Susan J.3,4; Yang, Li2,5 ; Preiss, Thomas 1,6
	2020-04-15
发表期刊	BMC BIOLOGY
EISSN	1741-7007
卷号	18 期号:1
发表状态	已发表
DOI	10.1186/s12915-020-00769-5
摘要	Background 5-Methylcytosine (m(5)C) is a prevalent base modification in tRNA and rRNA but it also occurs more broadly in the transcriptome, including in mRNA, where it serves incompletely understood molecular functions. In pursuit of potential links of m(5)C with mRNA translation, we performed polysome profiling of human HeLa cell lysates and subjected RNA from resultant fractions to efficient bisulfite conversion followed by RNA sequencing (bsRNA-seq). Bioinformatic filters for rigorous site calling were devised to reduce technical noise. Results We obtained similar to 1000 candidate m(5)C sites in the wider transcriptome, most of which were found in mRNA. Multiple novel sites were validated by amplicon-specific bsRNA-seq in independent samples of either human HeLa, LNCaP and PrEC cells. Furthermore, RNAi-mediated depletion of either the NSUN2 or TRDMT1 m(5)C:RNA methyltransferases showed a clear dependence on NSUN2 for the majority of tested sites in both mRNAs and noncoding RNAs. Candidate m(5)C sites in mRNAs are enriched in 5 ' UTRs and near start codons and are embedded in a local context reminiscent of the NSUN2-dependent m(5)C sites found in the variable loop of tRNA. Analysing mRNA sites across the polysome profile revealed that modification levels, at bulk and for many individual sites, were inversely correlated with ribosome association. Conclusions Our findings emphasise the major role of NSUN2 in placing the m(5)C mark transcriptome-wide. We further present evidence that substantiates a functional interdependence of cytosine methylation level with mRNA translation. Additionally, we identify several compelling candidate sites for future mechanistic analysis.
关键词	Epitranscriptome RNA methylation 5-Methylcytosine NSUN2 TRDMT1 Bisulfite conversion Bisulfite RNA-seq RNA stability mRNA translation Polysome
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收录类别	SCI ; SCIE
语种	英语
资助项目	National Natural Science Foundation of China (NSFC)[31925011] ; National Natural Science Foundation of China (NSFC)[91940306]
WOS研究方向	Life Sciences & Biomedicine - Other Topics
WOS类目	Biology
WOS记录号	WOS:000528947000001
出版者	BMC
WOS关键词	RIBOSOMAL-RNA ; R PACKAGE ; METHYLATION ; IDENTIFICATION ; EXPRESSION ; BISULFITE ; STRESS ; M(5)C ; 5-HYDROXYMETHYLCYTOSINE ; EPITRANSCRIPTOMICS
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/119530
专题	生命科学与技术学院_特聘教授组_杨力组
通讯作者	Preiss, Thomas
作者单位	1.Australian Natl Univ, John Curtin Sch Med Res, Dept Genome Sci, EMBL Australia Collaborating Grp, Canberra, ACT 2601, Australia 2.Chinese Acad Sci, Shanghai Inst Nutr & Hlth, CAS Key Lab Computat Biol, Univ Chinese Acad Sci,Shanghai Inst Biol Sci,CAS, Shanghai 200031, Peoples R China 3.Garvan Inst Med Res, Genom & Epigenet Div, Sydney, NSW 2010, Australia 4.Univ New South Wales, Fac Med, St Vincents Clin Sch, Sydney, NSW 2010, Australia 5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 6.Victor Chang Cardiac Res Inst, Sydney, NSW 2010, Australia
推荐引用方式 GB/T 7714	Schumann, Ulrike,Zhang, He-Na,Sibbritt, Tennille,et al. Multiple links between 5-methylcytosine content of mRNA and translation[J]. BMC BIOLOGY,2020,18(1).
APA	Schumann, Ulrike.,Zhang, He-Na.,Sibbritt, Tennille.,Pan, Anyu.,Horvath, Attila.,...&Preiss, Thomas.(2020).Multiple links between 5-methylcytosine content of mRNA and translation.BMC BIOLOGY,18(1).
MLA	Schumann, Ulrike,et al."Multiple links between 5-methylcytosine content of mRNA and translation".BMC BIOLOGY 18.1(2020).