The Pat1-Lsm Complex Stabilizes ATG mRNA during Nitrogen Starvation-Induced Autophagy
The Pat1-Lsm Complex Stabilizes ATG mRNA during Nitrogen Starvation-Induced Autophagy
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DOI：
10.1016/j.molcel.2018.11.002
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发表时间：
2019-01-17
期刊：
影响因子：
16
通讯作者：
Klionsky, Daniel J.
中科院分区：
文献类型：
--
作者：
Gatica, Damian;Hu, Guowu;Klionsky, Daniel J.
巨自噬/自噬是一种关键的分解代谢循环途径，需要微调调节以预防病理并保持体内平衡。在这里，我们报告了一种新的转录后通路调节自噬，涉及 Pat1-Lsm（Lsm1 至 Lsm7）mRNA 结合复合物。在氮饥饿条件下，Pat1-Lsm 结合自噬相关 (ATG) 转录本的特定子集，并防止外泌体复合物对其 3' 至 5' 进行降解，从而导致 ATG mRNA 稳定和积累。该过程通过 Pat1 去磷酸化进行调节，对于特定 Atg 蛋白的有效表达是必需的，并且是氮饥饿期间强大的自噬诱导所必需的。据我们所知，这项工作提出了通过 3' 结合因子和外泌体降解进行 ATG 转录调控的第一个例子。
Macroautophagy/autophagy is a key catabolic recycling pathway that requires fine-tuned regulation to prevent pathologies and preserve homeostasis. Here, we report a new post-transcriptional pathway regulating autophagy involving the Pat1-Lsm (Lsm1 to Lsm7) mRNA-binding complex. Under nitrogen-starvation conditions, Pat1-Lsm binds a specific subset of autophagy-related (ATG) transcripts and prevents their 3' to 5' degradation by the exosome complex, leading to ATG mRNA stabilization and accumulation. This process is regulated through Pat1 dephosphorylation, is necessary for the efficient expression of specific Atg proteins, and is required for robust autophagy induction during nitrogen starvation. To the best of our knowledge, this work presents the first example of ATGtranscript regulation via 3' binding factors and exosomal degradation.