Despite the central role of iron in biology, our understanding of how cells sense iron is limited to protein-dependent mechanisms. Here, we report the discovery of iron-sensing riboswitches (named Sensei). Present across bacterial phyla, these RNAs reside in the 5′ untranslated regions or within coding regions of messenger RNAs (mRNAs) encoding iron-related proteins. These riboswitches bind the reduced form of iron with high specificity. Iron binding causes conformational changes in the riboswitch that alter the accessibility of conserved nucleotides, ultimately enabling a genetic response. Sensei–iron interactions result in increased translation of the riboswitch-associated mRNA in vivo, thus positioning these riboswitches as true metalloregulators. Learning from natural Sensei RNAs, we engineer metal selectivity, successfully converting a nickel/cobalt sensing riboswitch to exclusively bind iron and a Sensei RNA to now exclusively recognize cobalt. We thus define the sequence and structural space of iron-sensing RNAs and open avenues for the design of RNA-based biosensors.

尽管铁在生物学中发挥着核心作用，但我们对细胞如何感知铁的理解仅限于蛋白质依赖性机制。在这里，我们报告了铁感应核糖开关（名为 Sensei）的发现。这些 RNA 存在于细菌门中，位于编码铁相关蛋白的信使 RNA (mRNA) 的 5' 非翻译区或编码区内。这些核糖开关以高特异性结合还原形式的铁。铁结合会引起核糖开关的构象变化，从而改变保守核苷酸的可及性，最终实现遗传反应。 Sensei-铁相互作用导致体内核糖开关相关 mRNA 的翻译增加，从而将这些核糖开关定位为真正的金属调节剂。借鉴天然 Sensei RNA 的经验，我们设计了金属选择性，成功地将镍/钴传感核糖开关转化为专门结合铁，并将 Sensei RNA 转化为专门识别钴。因此，我们定义了铁传感 RNA 的序列和结构空间，并为基于 RNA 的生物传感器的设计开辟了途径。