APOBEC3A regulates transcription from interferon-stimulated response elements

Abstract

Significance APOBEC3A (A3A) is a DNA binding enzyme that introduces mutations through its cytidine deaminase activity. In addition, A3A can repress proviral HIV-1 and retroelements within the host genome by a deaminase-independent mechanism. Here, we demonstrate that A3A binds to the promoter sequence of interferon (IFN)-stimulated gene (ISG)15 and suppresses IFN-stimulated response element activity. In a deaminase-independent manner, A3A reduces ISG15 expression in response to IFN stimulation. A3A overexpression decreases and A3A knockout increases the expression of several ISGs in response to IFN-α treatment. Since A3A itself is an ISG, our data suggest that A3A plays a role in a negative feedback loop to control ISG expression.

Single‐cell transcriptome analysis reveals keratinocyte subpopulations contributing to psoriasis in corneum and granular layer

“…This study revealed that subsets 0, 1, 2, 4, 7, and 9 of keratinocytes in the stratum corneum exhibited elevated gene expression levels in the psoriasis group. Notably, subset 0 (Figure 4A) exhibited a high expression of APOBEC3A, 11 a cytidine deaminase known for its role in inactivating various viruses by introducing lethal mutations into the viral genome. In subset 1 (Figure 4B), the genes MTRNR2L12, MTRNR2L1, and MTRNR2L8 were upregulated.…”

APOBECs: Our fickle friends?

“…However, induction of the hA3 enzymes has been documented in multiple myeloid and lymphocyte lineages, which quickly encounter invading pathogens [ 8 ]. Recent work has suggested that human A3A competes for binding to IFN-stimulated regulatory elements (ISREs) found upstream of a subset of genes, perhaps providing a feedback loop to dampen innate immune responses after initial pathogen encounters [ 41 ]. Therefore, although APOBECs provide friendly antiviral functions, their activity appears to be deleterious if unregulated, similar to other immune responses.…”

Differentiation signals induce APOBEC3A expression via GRHL3 in squamous epithelia and squamous cell carcinoma

“…The APOBEC3 enzymes convert deoxycytidine to deoxyuridine in single-stranded DNA (ssDNA), a mutagenic activity that explains at least in part their ability to restrict replication of retroviruses and endogenous retroelements through targeting nascent cDNA during reverse transcription 1,2 . In addition, APOBEC3A and APOBEC3B have evolved functions in the cell nucleus including transcriptional regulation 3,4 and responses to nuclear-resident viruses [5][6][7][8][9][10] . Acquisition of these nuclear functions appears to have come at a cost however, as both APOBEC3A and APOBEC3B have been implicated in generating somatic mutations (mainly C>T transitions and C>G tranversions at TpC sites) in cancer cell genomes, driving cancer development and therapeutic resistance [11][12][13][14][15][16][17][18][19][20][21][22] .…”