Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA; Department of Microbiology, New York University School of Medicine, 430 E. 29th Street, New York, NY 10016, USA.
Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA; Department of Microbiology, New York University School of Medicine, 430 E. 29th Street, New York, NY 10016, USA.
Mol Cell. 2021 Jan 7;81(1):127-138.e4. doi: 10.1016/j.molcel.2020.10.025. Epub 2020 Nov 18.
Riboswitches are thought generally to function by modulating transcription elongation or translation initiation. In rare instances, ligand binding to a riboswitch has been found to alter the rate of RNA degradation by directly stimulating or inhibiting nearby cleavage. Here, we show that guanidine-induced pseudoknot formation by the aptamer domain of a guanidine III riboswitch from Legionella pneumophila has a different effect, stabilizing mRNA by protecting distal cleavage sites en masse from ribonuclease attack. It does so by creating a coaxially base-paired obstacle that impedes scanning from a monophosphorylated 5' end to those sites by the regulatory endonuclease RNase E. Ligand binding by other riboswitch aptamers peripheral to the path traveled by RNase E does not inhibit distal cleavage. These findings reveal that a riboswitch aptamer can function independently of any overlapping expression platform to regulate gene expression by acting directly to prolong mRNA longevity in response to ligand binding.
核糖开关通常被认为通过调节转录延伸或翻译起始来发挥作用。在极少数情况下，已经发现配体与核糖开关的结合通过直接刺激或抑制附近的切割来改变 RNA 降解的速率。在这里，我们表明，来自嗜肺军团菌的胍 III 核糖开关的适体结构域诱导胍诱导的假结形成具有不同的作用，通过保护远距离切割位点免受核糖核酸酶攻击来稳定 mRNA。它通过创建一个共轴碱基配对的障碍物来实现，该障碍物阻止了从单磷酸化的 5'末端到 RNase E 调控内切核酸酶的那些位点的扫描。与 RNase E 行进路径相邻的其他核糖开关适体的配体结合不会抑制远距离切割。这些发现表明，核糖开关适体可以独立于任何重叠的表达平台发挥作用，通过直接作用来延长 mRNA 的寿命，以响应配体结合来调节基因表达。
