Creative Research Initiatives Center for Molecular Biology of Translation, Korea University, Seoul, 02841, Republic of Korea.
Division of Life Sciences, Korea University, Seoul, 02841, Republic of Korea.
Nat Commun. 2022 Mar 17;13(1):1436. doi: 10.1038/s41467-022-29139-1.
LC3/ATG8 has long been appreciated to play a central role in autophagy, by which a variety of cytoplasmic materials are delivered to lysosomes and eventually degraded. However, information on the molecular functions of LC3 in RNA biology is very limited. Here, we show that LC3B is an RNA-binding protein that directly binds to mRNAs with a preference for a consensus AAUAAA motif corresponding to a polyadenylation sequence. Autophagic activation promotes an association between LC3B and target mRNAs and triggers rapid degradation of target mRNAs in a CCR4-NOT-dependent manner before autolysosome formation. Furthermore, our transcriptome-wide analysis reveals that PRMT1 mRNA, which encodes a negative regulator of autophagy, is one of the major substrates. Rapid degradation of PRMT1 mRNA by LC3B facilitates autophagy. Collectively, we demonstrate that LC3B acts as an RNA-binding protein and an mRNA decay factor necessary for efficient autophagy.
LC3/ATG8 长期以来被认为在自噬中发挥核心作用，通过自噬，各种细胞质物质被递送到溶酶体并最终被降解。然而，关于 LC3 在 RNA 生物学中的分子功能的信息非常有限。在这里，我们表明 LC3B 是一种 RNA 结合蛋白，它直接与 mRNA 结合，对与多聚腺苷酸化序列相对应的共识 AAUAAA 基序有偏好。自噬激活促进 LC3B 与靶 mRNA 之间的结合，并在自噬溶酶体形成之前以 CCR4-NOT 依赖性方式触发靶 mRNA 的快速降解。此外，我们的全转录组分析表明，编码自噬负调节剂的 PRMT1 mRNA 是主要底物之一。LC3B 对 PRMT1 mRNA 的快速降解促进了自噬。总之，我们证明 LC3B 作为一种 RNA 结合蛋白和一种 mRNA 降解因子，对于有效的自噬是必需的。
