Thongdee Narumon, Alaniz Miranda M, Samatova Ekaterina, Zhong Aoshu, Esnault Caroline, Zhang Hongen, Dale Ryan K, Rodnina Marina V, Storz Gisela
Division of Molecular and Cellular Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 20892, USA.
Max Planck Institute for Multidisciplinary Sciences, Department of Physical Biochemistry, 37077 Göttingen, Germany.
Mol Cell. 2025 May 1;85(9):1824-1837.e7. doi: 10.1016/j.molcel.2025.03.014. Epub 2025 Apr 7.
Most characterized interactions between bacterial small RNAs (sRNAs) and their target mRNAs occur near ribosome binding sites, resulting in changes in translation initiation or target mRNA decay. To understand the consequences of sRNA pairing internal to coding sequences detected by global RNA-RNA interactome approaches, we examined the impact of sRNA overexpression on seven target proteins. Overexpression of the sRNA led to decreased target protein levels for two pairs, but there were no differences for the others. By further examining ArcZ-ligA and ArcZ-hemK, we discovered that ArcZ pairing with the mRNAs leads to translation pausing and increased protein activity. A ligA point mutation that eliminates sRNA pairing resulted in increased sensitivity to DNA damage, revealing the physiological consequences of the regulation. Thus, regulatory RNA pairing in coding sequences can locally slow translation elongation, likely impacting co-translational protein folding and allowing improved incorporation of co-factors or more optimal folding under specific conditions.
大多数已表征的细菌小RNA（sRNA）与其靶mRNA之间的相互作用发生在核糖体结合位点附近，导致翻译起始或靶mRNA降解发生变化。为了了解通过全局RNA-RNA相互作用组方法检测到的编码序列内部sRNA配对的后果，我们研究了sRNA过表达对七种靶蛋白的影响。sRNA的过表达导致两对靶蛋白水平降低，但其他对没有差异。通过进一步研究ArcZ-ligA和ArcZ-hemK，我们发现ArcZ与mRNA配对会导致翻译暂停并增加蛋白质活性。消除sRNA配对的ligA点突变导致对DNA损伤的敏感性增加，揭示了这种调控的生理后果。因此，编码序列中的调控RNA配对可以局部减缓翻译延伸，可能影响共翻译蛋白质折叠，并允许在特定条件下更好地结合辅因子或实现更优化的折叠。
