Kellogg Morgana K, Tikhonova Elena B, Karamyshev Andrey L
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX, United States.
Front Genet. 2022 Jun 8;13:898083. doi: 10.3389/fgene.2022.898083. eCollection 2022.
The signal recognition particle (SRP) is a ribonucleoprotein complex with dual functions. It co-translationally targets proteins with a signal sequence to the endoplasmic reticulum (ER) and protects their mRNA from degradation. If SRP is depleted or cannot recognize the signal sequence, then the Regulation of Aberrant Protein Production (RAPP) is activated, which results in the loss of secretory protein mRNA. If SRP recognizes the substrates but is unable to target them to ER, they may mislocalize or degrade. All these events lead to dramatic consequence for protein biogenesis, activating protein quality control pathways, and creating pressure on cell physiology, and might lead to the pathogenesis of disease. Indeed, SRP dysfunction is involved in many different human diseases, including: congenital neutropenia; idiopathic inflammatory myopathy; viral, protozoal, and prion infections; and cancer. In this work, we analyze diseases caused by SRP failure and discuss their possible molecular mechanisms.
信号识别颗粒（SRP）是一种具有双重功能的核糖核蛋白复合体。它在共翻译过程中将带有信号序列的蛋白质靶向内质网（ER），并保护其mRNA不被降解。如果SRP缺失或无法识别信号序列，那么异常蛋白质产生调节（RAPP）就会被激活，这会导致分泌蛋白mRNA的丢失。如果SRP识别底物但无法将它们靶向内质网，它们可能会定位错误或降解。所有这些事件都会对蛋白质生物合成产生重大影响，激活蛋白质质量控制途径，并给细胞生理造成压力，还可能导致疾病的发病机制。事实上，SRP功能障碍涉及许多不同的人类疾病，包括：先天性中性粒细胞减少症；特发性炎性肌病；病毒、原生动物和朊病毒感染；以及癌症。在这项工作中，我们分析了由SRP功能衰竭引起的疾病，并讨论了其可能的分子机制。
