RNA structure maps across mammalian cellular compartments

被引:186
作者
Sun, Lei [1 ,2 ,3 ,4 ]
Fazal, Furqan M. [5 ,6 ,7 ]
Li, Pan [1 ,2 ,3 ,4 ]
Broughton, James P. [5 ,6 ,7 ]
Lee, Byron [5 ,6 ,7 ]
Tang, Lei [1 ,2 ,3 ,4 ]
Huang, Wenze [1 ,2 ,3 ,4 ]
Kool, Eric T. [8 ]
Chang, Howard Y. [5 ,6 ,7 ,9 ]
Zhang, Qiangfeng Cliff [1 ,2 ,3 ,4 ]
机构
[1] Tsinghua Univ, Sch Life Sci, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China
[2] Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Beijing Frontier Res Ctr Biol Struct, Beijing 100084, Peoples R China
[3] Tsinghua Univ, Ctr Synthet & Syst Biol, Beijing 100084, Peoples R China
[4] Tsinghua Univ, Tsinghua Peking Joint Ctr Life Sci, Beijing 100084, Peoples R China
[5] Stanford Univ, Ctr Personal Dynam Regulomes, Stanford, CA 94305 USA
[6] Stanford Univ, Dept Dermatol, Stanford, CA 94305 USA
[7] Stanford Univ, Dept Genet, Stanford, CA 94305 USA
[8] Stanford Univ, Dept Chem, Stanford, CA 94305 USA
[9] Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA
基金
中国国家自然科学基金;
关键词
SECONDARY STRUCTURE; GENE-EXPRESSION; CELLS REVEALS; LIVING CELLS; TRANSCRIPTOME; N-6-METHYLADENOSINE; TRANSLATION; POLYMERASE; DYNAMICS; LOCALIZATION;
D O I
10.1038/s41594-019-0200-7
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
RNA structure is intimately connected to each step of gene expression. Recent advances have enabled transcriptome-wide maps of RNA secondary structure, called 'RNA structuromes'. However, previous whole-cell analyses lacked the resolution to unravel the landscape and also the regulatory mechanisms of RNA structural changes across subcellular compartments. Here we reveal the RNA structuromes in three compartments, chromatin, nucleoplasm and cytoplasm, in human and mouse cells. The cytotopic structuromes substantially expand RNA structural information and enable detailed investigation of the central role of RNA structure in linking transcription, translation and RNA decay. We develop a resource with which to visualize the interplay of RNA-protein interactions, RNA modifications and RNA structure and predict both direct and indirect reader proteins of RNA modifications. We also validate a novel role for the RNA-binding protein LIN28A as an N-6-methyladenosine modification 'antireader'. Our results highlight the dynamic nature of RNA structures and its functional importance in gene regulation.
引用
收藏
页码:322 / +
页数:14
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