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Ubiquitous HEPN domain-containing proteins harbor a conserved RNase motif and are found in both prokaryotes and eukaryotes. In prokaryotes, HEPN domain toxins frequently pair with adjacent MNT domain antitoxins to form the prevalent type VII HepT\/MntA toxin-antitoxin (TA) system. Here, we identified a group of fused MNT-HEPN proteins (renamed FhepTA) carried by mobile genetic elements in the Shewanella genus; these proteins show high similarity to the HepT\/MntA TA systems. When encoded as separate genes, the MntA antitoxin oligoAMPylates the HEPN domain toxin HepT to block its toxicity. While FhepTA toxicity is also blocked by oligoAMPylation, it is additionally regulated by a redox switch involving two unique cysteines within its HEPN domain. Furthermore, the N-terminal MNT domain intrinsically inhibits toxicity by preventing dimerization of the C-terminal HEPN domain. Thus, the fused MNT-HEPN architecture represents a new family of TA modules potentially regulated in both ATP-dependent (via oligoAMPylation) and redox-state-dependent oligomerization.<\/jats:p>","DOI":"10.1093\/nar\/gkag228","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T09:29:23Z","timestamp":1773912563000},"source":"Crossref","is-referenced-by-count":1,"title":["Dual regulation of HEPN RNase in fused MNT-HEPN toxin-antitoxin systems via protein OligoAMPylation and oligomerization"],"prefix":"10.1093","volume":"54","author":[{"given":"Jianyun","family":"Yao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Tropical Oceanography, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences , No.1119, Haibin Road, Nansha District, Guangzhou 511458 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Tropical Oceanography, Guangdong Key Laboratory of Marine Materia Medica, South China Sea Institute of Oceanology, Chinese Academy of Sciences , No.1119, Haibin Road, Nansha District, Guangzhou 511458 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangkai","family":"Zhen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Microbial Pathogenesis and Interventions of Fuian Province University, College of Life Sciences, Fujian Normal University , Fuzhou 350117 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanghai Cell Therapy Group Co. , Ltd, Shanghai 201805 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