Landscape of adenosine-to-inosine RNA recoding across human tissues

被引:66
作者
Gabay, Orshay [1 ]
Shoshan, Yoav [2 ,3 ]
Kopel, Eli [1 ]
Ben-Zvi, Udi [1 ]
Mann, Tomer D. [4 ,5 ]
Bressler, Noam [2 ,3 ]
Cohen-Fultheim, Roni [1 ]
Schaffer, Amos A. [1 ]
Roth, Shalom Hillel [1 ]
Tzur, Ziv [1 ]
Levanon, Erez Y. [1 ,6 ]
Eisenberg, Eli [2 ,3 ]
机构
[1] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-5290002 Ramat Gan, Israel
[2] Tel Aviv Univ, Raymond & Beverly Sackler Sch Phys & Astron, IL-6997801 Tel Aviv, Israel
[3] Tel Aviv Univ, Sagol Sch Neurosci, IL-6997801 Tel Aviv, Israel
[4] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel
[5] Tel Aviv Univ, Sackler Sch Med, Tel Aviv, Israel
[6] Bar Ilan Univ, Inst Nanotechnol & Adv Mat, IL-5290002 Ramat Gan, Israel
基金
芬兰科学院; 以色列科学基金会;
关键词
MESSENGER-RNA; EDITING SITES; HUMAN BRAIN; IDENTIFICATION; TRANSCRIPTOME; EXPRESSION; GENE; MASS; ALU; DEAMINASES;
D O I
10.1038/s41467-022-28841-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Gabay et al. provide a highly-accurate atlas of recoding by A-to-I RNA editing in human, profiled across tissues and cell subpopulations. Most highly edited sites are evolutionary conserved in non-primate mammals, attesting for adaptation. RNA editing by adenosine deaminases changes the information encoded in the mRNA from its genomic blueprint. Editing of protein-coding sequences can introduce novel, functionally distinct, protein isoforms and diversify the proteome. The functional importance of a few recoding sites has been appreciated for decades. However, systematic methods to uncover these sites perform poorly, and the full repertoire of recoding in human and other mammals is unknown. Here we present a new detection approach, and analyze 9125 GTEx RNA-seq samples, to produce a highly-accurate atlas of 1517 editing sites within the coding region and their editing levels across human tissues. Single-cell RNA-seq data shows protein recoding contributes to the variability across cell subpopulations. Most highly edited sites are evolutionary conserved in non-primate mammals, attesting for adaptation. This comprehensive set can facilitate understanding of the role of recoding in human physiology and diseases.
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页数:17
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