Poster abstracts
Poster number 134 submitted by Shraddha Sharma
Identification of APOBEC3A as an RNA editing enzyme
Shraddha Sharma (Dept. of Pathology, Roswell Park Cancer Institute), Santosh K. Patnaik (Dept. of Thoracic surgery, Roswell Park Cancer Institute), Robert T. Taggart (Dept. of Pathology, Roswell Park Cancer Institute), Sally M. Enriquez (Dept. of Biological Sciences, SUNY Buffalo), Paul Gollnick (Dept. of Biological Sciences, SUNY Buffalo), Bora E. Baysal (Dept. of Pathology, Roswell Park Cancer Institute)
Abstract:
RNA editing co- or post transcriptionally alters RNA transcripts encoded by DNA. Aberrant RNA editing is implicated in the pathogenesis of cancer and neurodegenerative disorders. A-to-I and C-to-U editing are the two most common types of RNA editing in mammals. RNA-dependent adenosine deaminases ADAR1, ADAR2 and ADAR3, and APOBEC1, a cytidine deaminase, are the only known RNA editing enzymes in mammals. Unlike A-to-I RNA editing, the regulation, extent and enzymatic basis of C-to-U RNA editing is poorly understood.
We previously identified hypoxia-inducible site-specific C-to-U editing in SDHB RNA, which encodes a catalytic subunit of succinate dehydrogenase. To identify additional RNA editing events, we analyzed transcriptome-wide sequence data from primary monocytes exposed to hypoxia. In addition, we analyzed transcriptome-wide sequence data from monocyte-derived macrophages and investigated the correlation of SDHB RNA editing with expression of cytidine deaminase enzymes in certain common tumors in The Cancer Genome Atlas. We found site-specific C-to-U editing in transcripts of hundreds of genes in human monocytes and macrophages, including many that are involved in the pathogenesis of viral diseases. Such editing is induced by low oxygen (hypoxia) and interferon in monocytes and also during M1 macrophage polarization. We demonstrate for the first time that APOBEC3A is responsible for RNA editing.
Our findings significantly expand our knowledge of C-to-U RNA editing events, uncover for the first time a role for micro-environment in inducing RNA editing, and reveals the previously unrecognized RNA editing activity of the APOBEC3A cytidine deaminase in innate immune cells.
References:
Sharma, S. et al. APOBEC3A cytidine deaminase induces RNA editing in monocytes and macrophages. Nature communications 6 (2015).
Sharma, S., Patnaik, S. K., Kemer, Z. & Baysal, B. E. Transient overexpression of exogenous APOBEC3A causes C-to-U RNA editing of thousands of genes. RNA biology, 00-00 (2016).
Keywords: RNA editing, APOBEC3A, immune cells