ABSTRACT

Adipogenesis is regulated by genetic interactions, in which post-transcriptional regulation plays an important role. Staufen double-stranded RNA binding protein 1 (Staufen1 or STAU1) plays diverse roles in RNA processing and adipogenesis. Previously, we found that the downregulation of STAU1 affects the expression of fatty acid-binding protein 4 (FABP4) at the protein level but not at the mRNA level. This study aimed to determine the mechanism underlying the regulation of FABP4 expression by STAU1, explaining the inconsistency between FABP4 mRNA and protein levels. We used RNA interference, photoactivatable ribonucleoside enhanced cross-linking and immunoprecipitation, and an adeno-associated virus to examine the functions of STAU1 in adipogenesis. Our results indicate that STAU1 binds to the coding sequences of FABP4, thereby regulating the translation of FABP4 mRNA by unwinding the double-stranded structure. Furthermore, STAU1 mediates adipogenesis by regulating the secretion of free fatty acids. However, STAU1 knockdown decreases the fat weight/body weight ratio but does not affect the plasma triglyceride levels. These findings describe the mechanisms involved in STAU1-mediated regulation of FABP4 expression at the translational level during adipogenesis.

摘要

脂肪生成受遗传相互作用的调节，其中转录后调节起着重要作用。Staufen 双链 RNA 结合蛋白 1（Staufen1 或STAU1）在 RNA 加工和脂肪生成中发挥着不同的作用。此前，我们发现STAU1的下调影响蛋白质水平的脂肪酸结合蛋白 4 (FABP4) 的表达，但不影响 mRNA 水平的表达。本研究旨在确定 STAU1 调节 FABP4 表达的机制，解释 FABP4 mRNA 和蛋白质水平之间的不一致。我们使用 RNA 干扰、可光活化核糖核苷增强交联和免疫沉淀以及腺相关病毒来检查 STAU1 在脂肪生成中的功能。我们的结果表明 STAU1 与 FABP4 的编码序列结合，从而调节FABP4的翻译mRNA通过解开双链结构。此外，STAU1 通过调节游离脂肪酸的分泌来介导脂肪生成。然而，STAU1 敲低降低了脂肪重量/体重比，但不影响血浆甘油三酯水平。这些发现描述了在脂肪生成过程中，STAU1 介导的FABP4表达在翻译水平上的调节所涉及的机制。