Dynamics of diversified A-to-I editing in Streptococcus pyogenes is governed by changes in mRNA stability. A-to-I editing in Streptococcus pyogenes

Adenosine-to-inosine (A-to-I) RNA editing plays an important role in the post-transcriptional regulation of eukaryotic cell physiology. However, our understanding of the occurrence, function, and regulation of A-to-I editing in bacteria remains limited. Bacterial mRNA editing is catalysed by the deaminase TadA, that was originally described to modify a single tRNA in E. coli. Intriguingly, several bacterial species appear to perform A-to-I editing on more than one tRNA. Here, we provide evidence that in the human pathogen Streptococcus pyogenes tRNA editing expanded to an additional tRNA substrate. Utilizing RNA sequencing, we identified more than 27 editing sites in the transcriptome of S. pyogenes SF370 and demonstrate that the adaptation of S. pyogenes TadA to a second tRNA substrate also diversified the sequence context and recoding scope of mRNA editing. Based on the observation that editing is dynamically regulated in response to several infection-relevant stimuli, such as oxidative stress, we further investigated the underlying determinants of editing dynamics and identified mRNA stability as a key modulator of A-to-I editing. Overall, our findings reveal the presence and diversification of A-to-I editing in S. pyogenes and provide novel insights into editome plasticity and its regulation in bacteria.

腺苷脱氨至肌苷（A-to-I）RNA编辑在真核细胞生理过程的转录后调控中发挥着重要作用。然而，目前学界对细菌中A-to-I编辑的发生、功能及调控机制的认知仍较为有限。细菌信使RNA（mRNA）编辑由脱氨酶TadA催化，该酶最初被报道可修饰大肠杆菌（E. coli）中的单一转运RNA（tRNA）。值得注意的是，已有研究显示多种细菌可对多于一种的tRNA进行A-to-I编辑。本研究证实，在人类病原体酿脓链球菌（Streptococcus pyogenes）中，tRNA编辑的底物范围扩展至了额外的一类tRNA底物。本研究通过RNA测序（RNA sequencing）技术，在酿脓链球菌SF370的转录组中鉴定出超过27个编辑位点，并证明酿脓链球菌TadA对第二种tRNA底物的适配，同时也使得mRNA编辑的序列上下文与重编码范围实现了多样化。基于编辑过程可响应多种感染相关刺激（如氧化应激）而被动态调控这一观察结果，我们进一步探究了编辑动态性的潜在决定因素，并证实mRNA稳定性是A-to-I编辑的关键调节因子。综上，本研究揭示了酿脓链球菌中A-to-I编辑的存在及其多样化特征，为细菌编辑组（editome）可塑性及其调控机制提供了全新的认知视角。