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