Lee Kyung-Ha
Department of Molecular Biology, Pusan National University, Busan, Republic of Korea.
Institute of Systems Biology, Pusan National University, Busan, Republic of Korea.
Anim Cells Syst (Seoul). 2023 Nov 14;27(1):321-328. doi: 10.1080/19768354.2023.2275613. eCollection 2023.
The internal ribosome entry site (IRES) is a unique structure found in the 5' untranslated region (5'-UTR) of specific messenger RNAs (mRNAs) that allows ribosomes to bind and initiate translation without the need for a cap structure. In this study, we investigated the presence and functional properties of the IRES activity of nitric oxide synthase 2 (NOS2) mRNA, which encodes an enzyme that produces nitric oxide in response to various stimuli such as inflammation. Nitric oxide is a signaling molecule that plays a crucial role in various physiological processes, including immune responses and neuronal signaling. Our results showed the existence of IRES activity in the 5'-UTR of Nos2 mRNA in various cell types. IRES-mediated translation of NOS2 mRNA was higher in neuronal cells and its activity increased in response to lipopolysaccharide (LPS). Despite inhibition of cap-dependent translation, nitrite production was partially maintained. These results demonstrate the presence of IRES activity in the 5'-UTR of NOS2 mRNA and suggest that IRES-mediated translation plays a key role in controlling nitric oxide production in response to LPS, an inflammatory stimulus.
内部核糖体进入位点(IRES)是一种独特的结构,存在于特定信使核糖核酸(mRNA)的5'非翻译区(5'-UTR),它使核糖体能够在无需帽结构的情况下结合并启动翻译。在本研究中,我们调查了一氧化氮合酶2(NOS2)mRNA的IRES活性的存在及功能特性,该mRNA编码一种在诸如炎症等各种刺激下产生一氧化氮的酶。一氧化氮是一种信号分子,在包括免疫反应和神经元信号传导在内的各种生理过程中发挥关键作用。我们的结果表明,在各种细胞类型的Nos2 mRNA的5'-UTR中存在IRES活性。IRES介导的NOS2 mRNA翻译在神经元细胞中更高,并且其活性在脂多糖(LPS)刺激下增加。尽管帽依赖性翻译受到抑制,但亚硝酸盐的产生仍部分得以维持。这些结果证明了NOS2 mRNA的5'-UTR中存在IRES活性,并表明IRES介导的翻译在响应炎症刺激LPS时控制一氧化氮产生中起关键作用。