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Alternative Polyadenylation of Malic Enzyme 1 Is Essential for Accelerated Adipogenesis
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2023-12-13 , DOI: 10.1021/acs.jafc.3c06289 Xuyong Qin 1 , Chaoqun Meng 1 , Chengping Li 1 , Wei Zhao 1 , Shizhong Ren 1 , Shujun Cao 1 , Guoli Zhou 1
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2023-12-13 , DOI: 10.1021/acs.jafc.3c06289 Xuyong Qin 1 , Chaoqun Meng 1 , Chengping Li 1 , Wei Zhao 1 , Shizhong Ren 1 , Shujun Cao 1 , Guoli Zhou 1
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Understanding the mechanism of adipogenesis is an important basis for improving meat quality traits of livestock. Alternative polyadenylation (APA) is a vital mechanism to regulate the expression of eukaryotic genes. However, how the individual APA functions in adipogenesis remains elusive. This study was intended to investigate the effect of malic enzyme 1 (ME1) APA on adipogenesis. Here, intracellular lipid droplets were stained using Oil red O. 3′ RACE was used to verify APA events of the ME1 gene. Interactions between ME1 3′ untranslated region (3′ UTR)-APA isoforms and miRNAs, as well as differential expression of isoforms, were examined using dual-luciferase reporter and molecular experiments. The mechanism of ME1 APA on adipogenesis was explored by gain and loss of function assays. In this study, two ME1 isoforms with different 3′ UTR lengths were detected during adipogenesis. Moreover, the ME1 isoform with a short 3′ UTR was significantly upregulated compared with the one with a long 3′ UTR. Mechanistically, only the long ME1 isoform was targeted by miR-153-3p to attenuate adipogenesis, while the short one escaped the regulation of miR-153-3p to accelerate adipogenesis. Our results reveal a novel mechanism of ME1 APA in regulating adipogenesis.
中文翻译：
苹果酸酶 1 的替代多聚腺苷酸化对于加速脂肪生成至关重要
了解脂肪生成机制是改善畜禽肉品质性状的重要基础。选择性多腺苷酸化（APA）是调节真核基因表达的重要机制。然而，单个 APA 在脂肪生成中如何发挥作用仍然难以捉摸。本研究旨在探讨苹果酸酶 1 (ME1) APA 对脂肪生成的影响。这里，使用油红O对细胞内脂滴进行染色。3'RACE用于验证ME1基因的APA事件。使用双荧光素酶报告基因和分子实验检查了 ME1 3' 非翻译区 (3' UTR)-APA 同工型和 miRNA 之间的相互作用以及同工型的差异表达。通过功能获得和丧失测定来探讨 ME1 APA 对脂肪生成的机制。在这项研究中，在脂肪形成过程中检测到了两种具有不同 3'UTR 长度的 ME1 亚型。此外，与具有长3'UTR的ME1亚型相比，具有短3'UTR的ME1亚型显着上调。从机制上讲，只有长的 ME1 异构体被 miR-153-3p 靶向，从而减弱脂肪生成，而短的 ME1 异构体则逃脱了 miR-153-3p 的调控，加速脂肪生成。我们的结果揭示了 ME1 APA 调节脂肪生成的新机制。
更新日期：2023-12-13
中文翻译：
苹果酸酶 1 的替代多聚腺苷酸化对于加速脂肪生成至关重要
了解脂肪生成机制是改善畜禽肉品质性状的重要基础。选择性多腺苷酸化（APA）是调节真核基因表达的重要机制。然而，单个 APA 在脂肪生成中如何发挥作用仍然难以捉摸。本研究旨在探讨苹果酸酶 1 (ME1) APA 对脂肪生成的影响。这里，使用油红O对细胞内脂滴进行染色。3'RACE用于验证ME1基因的APA事件。使用双荧光素酶报告基因和分子实验检查了 ME1 3' 非翻译区 (3' UTR)-APA 同工型和 miRNA 之间的相互作用以及同工型的差异表达。通过功能获得和丧失测定来探讨 ME1 APA 对脂肪生成的机制。在这项研究中，在脂肪形成过程中检测到了两种具有不同 3'UTR 长度的 ME1 亚型。此外，与具有长3'UTR的ME1亚型相比，具有短3'UTR的ME1亚型显着上调。从机制上讲，只有长的 ME1 异构体被 miR-153-3p 靶向，从而减弱脂肪生成，而短的 ME1 异构体则逃脱了 miR-153-3p 的调控，加速脂肪生成。我们的结果揭示了 ME1 APA 调节脂肪生成的新机制。
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