Transient overexpression of exogenous APOBEC3A causes C-to-U RNA editing of thousands of genes

Abstract

APOBEC3A cytidine deaminase induces site-specific C-to-U RNA editing of hundreds of genes in monocytes exposed to hypoxia and/or interferons and in pro-inflammatory macrophages. To examine the impact of APOBEC3A overexpression, we transiently expressed APOBEC3A in HEK293T cell line and performed RNA sequencing. APOBEC3A overexpression induces C-to-U editing at more than 4,200 sites in transcripts of 3,078 genes resulting in protein recoding of 1,110 genes. We validate recoding RNA editing of genes associated with breast cancer, hematologic neoplasms, amyotrophic lateral sclerosis, Alzheimer disease and primary pulmonary hypertension. These results highlight the fundamental impact of APOBEC3A overexpression on human transcriptome by widespread RNA editing.

The double-domain cytidine deaminase APOBEC3G is a cellular site-specific RNA editing enzyme

“…RNA editing gene targets was enriched for ontologies of methyltransferase activity, nuclear transport, DNA helicase and ubiquitin proteasome pathway (Supplementary Table S5). RNA editing at 90 sites was also catalyzed by A3A (Supplementary Table S6) which causes C>U RNA editing of 4,374 sites in the 293T overexpression system31. This finding suggests that although a small overlap exists among the edited sites of A3A and A3G, RNA editing targets of these two enzymes are largely distinct and that A3A has a broader target profile than A3G.…”

“…However, recently we described that APOBEC3A (A3A) induces widespread site-specific C-to-U (C>U) RNA editing of cellular transcripts in pro-inflammatory macrophages and in monocytes exposed to hypoxia and/or interferons30. We also showed that the RNA editing function of A3A can be recapitulated by transient overexpression of A3A in 293T cells which causes site-specific RNA editing of thousands of transcripts31. Moreover, the majority (75%) of genes that are RNA-edited in the 293T overexpression system are also edited in monocyte-enriched PBMCs (MEPs) exposed to hypoxia and interferon type 1.…”

C-to-U editing and site-directed RNA editing for the correction of genetic mutations

“…Interestingly, APOBEC3A (A3A), another member of the cytidine deaminase family that is structurally related to APOBEC1 and is expressed primarily in myeloid cells, including monocytes and macrophages, has been identified as a novel C-to-U RNA editing enzyme (27,28). A3A functions in the inhibition of retrotransposons and several viruses including HIV-1 (human immunodeficiency virus type 1), HTLV1 (human T-cell lymphotropic virus type 1), HPV (human papillomavirus), parvovirus, and hepatitis B.…”

“…A3A functions in the inhibition of retrotransposons and several viruses including HIV-1 (human immunodeficiency virus type 1), HTLV1 (human T-cell lymphotropic virus type 1), HPV (human papillomavirus), parvovirus, and hepatitis B. The transcripts of hundreds of genes, including implicated viral pathogenesis, Alzheimer's disease, peripheral blood monocytes exposed to hypoxia and/or interferons, and M1 (proinflammatory) macrophage differentiation, undergo site-specific C-to-U RNA editing (27,28).…”

Untitled

“…The APOBEC3 (A3) family of cytidine deaminases restricts endogenous retroelements thousands of genes undergo site-specific editing [Sharma et al, 2016a]. Furthermore, we 64 demonstrated site-specific editing of ssRNA with purified recombinant A3A in vitro, whereas 65 DNA editing is non-specific and occurs at multiple TC nucleotides (edited C underlined) 66 [Sharma et al, 2015].…”