Epitranscriptomic profiling across cell types reveals associations between APOBEC1-mediated RNA editing, gene expression outcomes, and cellular function.

TitleEpitranscriptomic profiling across cell types reveals associations between APOBEC1-mediated RNA editing, gene expression outcomes, and cellular function.
Publication TypeJournal Article
Year of Publication2017
AuthorsRayon-Estrada V, Harjanto D, Hamilton CE, Berchiche YA, Gantman EConn, Sakmar TP, Bulloch K, Gagnidze K, Harroch S, McEwen BS, F Papavasiliou N
JournalProc Natl Acad Sci U S A
Volume114
Issue50
Pagination13296-13301
Date Published2017 Dec 12
ISSN1091-6490
Abstract

Epitranscriptomics refers to posttranscriptional alterations on an mRNA sequence that are dynamic and reproducible, and affect gene expression in a similar way to epigenetic modifications. However, the functional relevance of those modifications for the transcript, the cell, and the organism remain poorly understood. Here, we focus on RNA editing and show that Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-1 (APOBEC1), together with its cofactor RBM47, mediates robust editing in different tissues. The majority of editing events alter the sequence of the 3'UTR of targeted transcripts, and we focus on one cell type (monocytes) and on a small set of highly edited transcripts within it to show that editing alters gene expression by modulating translation (but not RNA stability or localization). We further show that specific cellular processes (phagocytosis and transendothelial migration) are enriched for transcripts that are targets of editing and that editing alters their function. Finally, we survey bone marrow progenitors and demonstrate that common monocyte progenitor cells express high levels of APOBEC1 and are susceptible to loss of the editing enzyme. Overall, APOBEC1-mediated transcriptome diversification is required for the fine-tuning of protein expression in monocytes, suggesting an epitranscriptomic mechanism for the proper maintenance of homeostasis in innate immune cells.

DOI10.1073/pnas.1714227114
Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID29167373
PubMed Central IDPMC5740640
Grant ListF32 CA183318 / CA / NCI NIH HHS / United States
R01 CA098495 / CA / NCI NIH HHS / United States

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