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LC3B 在自噬中的作用作为一种 RNA 结合蛋白。

The role of LC3B in autophagy as an RNA-binding protein.

机构信息

Creative Research Initiatives Center for Molecular Biology of Translation, Korea University, Seoul, Republic of Korea.

Division of Life Sciences, Korea University, Seoul, Republic of Korea.

出版信息

Autophagy. 2023 Mar;19(3):1028-1030. doi: 10.1080/15548627.2022.2111083. Epub 2022 Aug 13.

Abstract

The hallmark of cellular events observed upon macroautophagic/autophagic induction is the conjugation of LC3B, one of the mammalian Atg8 homologs, with phosphatidylethanolamine. This conversion from LC3B-I (an unconjugated form) to LC3B-II (a conjugated form) is essential for phagophore expansion and formation of autophagosomes. Our recent study revealed that LC3B binds to RNAs with a preference for the consensus AAUAAA motif and recruits the CCR4-NOT deadenylase complex. Consequently, LC3B elicits rapid degradation of mRNAs, which we have termed as LC3B-mediated mRNA decay (LMD). LMD requires the conversion of LC3B-I to LC3B-II and occurs before the formation of autolysosomes. Furthermore, we identified mRNA, which encodes a protein that functions as a negative regulator of autophagy, as an LMD substrate. A failure of rapid degradation of mRNA via LMD results in inefficient autophagy. Thus, our study unravels an important role of LC3B in autophagy as an RNA-binding protein for efficient mRNA decay.

摘要

细胞自噬/自噬诱导时观察到的标志性事件是 LC3B 的缀合,LC3B 是哺乳动物 Atg8 同源物之一,与磷脂酰乙醇胺缀合。LC3B-I(未缀合形式)向 LC3B-II(缀合形式)的这种转化对于吞噬体的扩展和自噬体的形成至关重要。我们最近的研究表明,LC3B 优先与共识 AAUAAA 基序结合 RNA,并募集 CCR4-NOT 脱腺苷酸酶复合物。因此,LC3B 引发 mRNA 的快速降解,我们将其称为 LC3B 介导的 mRNA 降解 (LMD)。LMD 需要 LC3B-I 向 LC3B-II 的转化,并且发生在自溶酶体形成之前。此外,我们鉴定了 mRNA,其编码一种作为自噬负调节剂的蛋白质,作为 LMD 底物。由于 LMD 未能快速降解 mRNA,导致自噬效率低下。因此,我们的研究揭示了 LC3B 作为 RNA 结合蛋白在自噬中有效降解 mRNA 的重要作用。

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