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

Orshay Gabay, Yoav Shoshan, Eli Kopel, Udi Ben-Zvi, Tomer D. Mann, Noam Bressler, Roni Cohen‐Fultheim, Amos A. Schaffer, Shalom Hillel Roth, Ziv Tzur, Erez Y. Levanon, Eli Eisenberg

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

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.

Original languageEnglish
Article number1184
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - 4 Mar 2022

Bibliographical note

Publisher Copyright:
© 2022, The Author(s).

Funding

We thank the GTEx consortium for making their RNA sequencing data publicly available. We thank Ariel Feiglin and Ilana Buchumenski for their help. This research has been supported by the International Collaboration Grant from the Jacki and Bruce Barron Cancer Research Scholars’ Program, a partnership of the Israel Cancer Research Fund and City of Hope, as supported by The Harvey L. Miller Family Foundation [205467 to E.Y.L], and the Israel Science Foundation (grant numbers 1945/18 to E.E and 2039/20, 231/21 to E.Y.L.). We thank the GTEx consortium for making their RNA sequencing data publicly available. We thank Ariel Feiglin and Ilana Buchumenski for their help. This research has been supported by the International Collaboration Grant from the Jacki and Bruce Barron Cancer Research Scholars’ Program, a partnership of the Israel Cancer Research Fund and City of Hope, as supported by The Harvey L. Miller Family Foundation [205467 to E.Y.L], and the Israel Science Foundation (grant numbers 1945/18 to E.E and 2039/20, 231/21 to E.Y.L.).

FundersFunder number
GTEx
Israel Cancer Research Fund205467
Israel Science Foundation2039/20, 1945/18, 231/21

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