Sabharwal Dharmesh, Song Tianyan, Papenfort Kai, Wai Sun Nyunt
a Department of Molecular Biology; The Laboratory for Molecular Infection Medicine Sweden (MIMS) , Umeå Centre for Microbial Research (UCMR); Umeå University , Umeå , Sweden.
RNA Biol. 2015;12(2):186-96. doi: 10.1080/15476286.2015.1017211.
Small non-coding RNAs (sRNAs) are emerging regulatory elements in bacteria. The Vibrio cholerae sRNA VrrA has previously been shown to down-regulate outer membrane proteins (OmpA and OmpT) and biofilm matrix protein (RbmC) by base-pairing with the 5' region of the corresponding mRNAs. In this study, we present an additional target of VrrA in V. cholerae, the mRNA coding for the ribosome binding protein Vrp. Vrp is homologous to ribosome-associated inhibitor A (RaiA) of Escherichia coli which facilitates stationary phase survival through ribosome hibernation. We show that VrrA down-regulates Vrp protein synthesis by base-pairing to the 5' region of vrp mRNA and that the regulation requires the RNA chaperone protein, Hfq. We further demonstrate that Vrp is highly expressed during stationary phase growth and associates with the ribosome of V. cholerae. The effect of the Vrp protein in starvation survival is synergistic with that of the VC2530 protein, a homolog of the E. coli hibernation promoting factor HPF, suggesting a combined role for these proteins in ribosome hibernation in V. cholerae. Vrp and VC2530 are important for V. cholerae starvation survival under nutrient deficient conditions. While VC2530 is down-regulated in cells lacking vrrA, mutation of vrp results in VC2530 activation. This is the first report indicating a regulatory role for an sRNA, modulating stationary factors involved in bacterial ribosome hibernation.
小非编码RNA（sRNA）是细菌中新兴的调控元件。先前已证明霍乱弧菌sRNA VrrA通过与相应mRNA的5'区域碱基配对来下调外膜蛋白（OmpA和OmpT）和生物膜基质蛋白（RbmC）。在本研究中，我们提出了霍乱弧菌中VrrA的另一个靶标，即编码核糖体结合蛋白Vrp的mRNA。Vrp与大肠杆菌的核糖体相关抑制剂A（RaiA）同源，后者通过核糖体休眠促进稳定期存活。我们表明VrrA通过与vrp mRNA的5'区域碱基配对来下调Vrp蛋白合成，并且这种调控需要RNA伴侣蛋白Hfq。我们进一步证明Vrp在稳定期生长期间高度表达，并与霍乱弧菌的核糖体相关。Vrp蛋白在饥饿存活中的作用与VC2530蛋白（大肠杆菌休眠促进因子HPF的同源物）的作用协同，表明这些蛋白在霍乱弧菌核糖体休眠中具有联合作用。Vrp和VC2530在营养缺乏条件下对霍乱弧菌饥饿存活很重要。虽然在缺乏vrrA的细胞中VC2530被下调，但vrp的突变导致VC2530激活。这是第一份表明sRNA具有调控作用的报告，其调节参与细菌核糖体休眠的稳定期因子。
