Elias Eyal, Gifford Isaac, Didi Liron, Fargeon Ofir, Arad Danielle, Cohen-Pavon Rinat, Sorek Gil, Levin Liron, Melamed Dganit, Aspit Liam, Barrick Jeffrey E, Bar-Yaacov Dan
The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78751, United States.
Nucleic Acids Res. 2025 Jul 8;53(13). doi: 10.1093/nar/gkaf656.
Adenosine-to-inosine (A-to-I) messenger RNA (mRNA) editing can affect the sequence and function of translated proteins and has been extensively investigated in eukaryotes. However, the prevalence of A-to-I mRNA editing in bacteria, its governing regulatory principles, and its biological significance are poorly understood. Here, we show that A-to-I mRNA editing occurs in hundreds of transcripts across dozens of gammaproteobacterial species, with most edits predicted to recode protein sequences. Furthermore, we reveal conserved regulatory determinants controlling editing across gammaproteobacterial species. Using Acinetobacter baylyi as a model, we show that mutating TadA, the mediating enzyme, reduces editing across all sites. Conversely, overexpressing TadA resulted in the editing of >300 transcripts, attesting to the editing potential of TadA. Notably, we show for the first time, at the protein level, that normal levels of A-to-I mRNA editing lead to wild-type bacteria expressing two protein isoforms from a single gene. Finally, we show that a TadA mutant with deficient editing activity does not grow at high temperatures, suggesting that RNA editing has a functional role in bacteria. Our work reveals that A-to-I mRNA editing in bacteria is widespread and has the potential to reshape the bacterial transcriptome and proteome.
腺苷到次黄苷（A-to-I）信使核糖核酸（mRNA）编辑可影响翻译后蛋白质的序列和功能，并且已在真核生物中得到广泛研究。然而，人们对细菌中A-to-I mRNA编辑的普遍性、其调控原则及其生物学意义知之甚少。在此，我们表明A-to-I mRNA编辑发生在数十种γ-变形菌物种的数百个转录本中，大多数编辑预计会对蛋白质序列进行重新编码。此外，我们揭示了控制γ-变形菌物种间编辑的保守调控决定因素。以拜氏不动杆菌为模型，我们发现突变介导酶TadA会减少所有位点的编辑。相反，过表达TadA导致300多个转录本发生编辑，证明了TadA的编辑潜力。值得注意的是，我们首次在蛋白质水平上表明，正常水平的A-to-I mRNA编辑会导致野生型细菌从单个基因表达两种蛋白质异构体。最后，我们表明编辑活性不足的TadA突变体在高温下无法生长，这表明RNA编辑在细菌中具有功能作用。我们的研究揭示了细菌中的A-to-I mRNA编辑广泛存在，并且有可能重塑细菌转录组和蛋白质组。
