Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, China.
Ann N Y Acad Sci. 2022 Aug;1514(1):93-103. doi: 10.1111/nyas.14782. Epub 2022 May 4.
Adenine modifications, including m A, m A, APA, and A-to-I modifications, are the most impactful RNA modifications. These modifications are primarily produced by enzymes called writers. The main purpose of this study was to explore the cross-talk and potential roles of these writers in severe asthma. We found 13 RNA writers potentially related to severe asthma and three RNA modification patterns. Cluster 3 showed predominant neutrophil infiltration and C-type lectin receptor signaling; cluster 1 showed predominant innate immune cell infiltration and ubiquitin-proteasome system activation; and cluster 2 did not show obvious immune infiltration characteristics. We found that RNA modification writers modified immune cell-related genes and led to both accumulation of different immune cells in the airways and activation of a series of biological processes, which ultimately leads to severe asthma. TRMT6, WTAP, and TRMT6A were included in a random forest model as predictors. Cromoglicic acid, thioperamide, and fluvastatin were potential drugs for clusters 1, 2, and 3, respectively. We found that cross-talk of RNA modifications is significant in severe asthma, which provides insight into severe asthma pathogenesis and possible treatment avenues.
腺嘌呤修饰，包括 mA、m A、APA 和 A-to-I 修饰，是最具影响力的 RNA 修饰。这些修饰主要由称为作家的酶产生。本研究的主要目的是探索这些作家在严重哮喘中的相互作用和潜在作用。我们发现了 13 种可能与严重哮喘相关的 RNA 作家和三种 RNA 修饰模式。簇 3 显示主要的中性粒细胞浸润和 C 型凝集素受体信号；簇 1 显示主要的固有免疫细胞浸润和泛素-蛋白酶体系统激活；而簇 2 没有显示明显的免疫浸润特征。我们发现 RNA 修饰作家修饰免疫细胞相关基因，导致气道中不同免疫细胞的积累和一系列生物过程的激活，最终导致严重哮喘。TRMT6、WTAP 和 TRMT6A 被包含在随机森林模型中作为预测因子。色甘酸、噻哌酰胺和氟伐他汀分别是簇 1、2 和 3 的潜在药物。我们发现 RNA 修饰的串扰在严重哮喘中是显著的，这为严重哮喘的发病机制和可能的治疗途径提供了新的见解。
