Frame-shifted APOBEC3A encodes two alternative pro-apoptotic proteins that target the mitochondrial network

Vincent Caval (1) , Rodolphe Suspène (1) , Pierre Khalfi (1, 2) , Julien Gaillard (3, 4) , Grégory Caignard (5) , Damien Vitour (5) , Philippe Roingeard (3, 4) , Jean Pierre Vartanian (1) , Simon Wain-Hobson (1)

1 Rétrovirologie Moléculaire
2 ED515 - Ecole Doctorale Complexité du Vivant
3 MAVIVH - U1259 Inserm - CHRU Tours - Morphogénèse et antigénicité du VIH et du virus des Hépatites
4 UNIV Tours - Plateforme IBISA de Microscopie Electronique [CHRU de Tours]
5 VIRO - Virologie UMR1161

The human APOBEC3A (A3A) cytidine deaminase is a powerful DNA mutator enzyme recognized as a major source of somatic mutations in tumor cell genomes. However, there is a discrepancy between APOBEC3A mRNA levels after interferon stimulation in myeloid cells and A3A detection at the protein level. To understand this difference, we investigated the expression of two novel alternative "A3Alt" proteins encoded in the +1-shifted reading frame of the APOBEC3A gene. A3Alt-L and its shorter isoform A3Alt-S appear to be transmembrane proteins targeted to the mitochondrial compartment that induce membrane depolarization and apoptosis. Thus, the APOBEC3A gene represents a new example wherein a single gene encodes two pro-apoptotic proteins, A3A cytidine deaminases that target the genome and A3Alt proteins that target mitochondria.

Keywords: A3Alt; APOBEC3A; apoptosis; mitochondria

Domains: Life Sciences [q-bio]

Vincent Caval, Rodolphe Suspène, Pierre Khalfi, Julien Gaillard, Grégory Caignard, et al.. Frame-shifted APOBEC3A encodes two alternative pro-apoptotic proteins that target the mitochondrial network. Journal of Biological Chemistry, 2021, 297 (3), pp.101081. ⟨10.1016/j.jbc.2021.101081⟩. ⟨pasteur-03333737⟩