a Life Sciences Institute , University of Michigan , Ann Arbor , MI , USA.
b Laboratory of Clinical Immunology and Microbiology , National Institute of Allergy and Infectious Diseases , Bethesda , MD , USA.
Autophagy. 2019 Apr;15(4):750-751. doi: 10.1080/15548627.2019.1587262. Epub 2019 Mar 18.
Deregulation of macroautophagy/autophagy, a conserved catabolic recycling pathway, has been implicated in the onset and development of several diseases. While post-translational regulation of auto-phagy-related (Atg) proteins has been an important research focus leading to significant breakthroughs in understanding autophagy regulation, less is known about the post-transcriptional regulation of ATG transcripts. In a recent study we showed that, during nitrogen starvation, the RNA-binding complex Pat1-Lsm is involved in binding and preventing the 3' to 5' exosome-mediated degradation of a specific subset of ATG mRNAs. Dephosphorylation of Pat1 at residues S456 and S457 facilitates ATG mRNA binding, resulting in ATG mRNA accumulation, Atg protein synthesis and robust autophagy induction. In addition, we present evidence that these processes are conserved in human cells. These results further elucidate our understanding of the post-transcriptional mechanism necessary for efficient induction of autophagy during stress conditions.
自噬(macroautophagy/autophagy)是一种保守的分解代谢回收途径,其失调与多种疾病的发生和发展有关。虽然自噬相关(Atg)蛋白的翻译后调控一直是理解自噬调控的重要研究焦点,并取得了重大突破,但 ATG 转录本的转录后调控知之甚少。在最近的一项研究中,我们表明,在氮饥饿期间,RNA 结合复合物 Pat1-Lsm 参与结合和防止特定亚类 Atg mRNA 的 3' 到 5' 外切体介导的降解。Pat1 残基 S456 和 S457 的去磷酸化促进 Atg mRNA 结合,导致 Atg mRNA 积累、Atg 蛋白合成和强烈的自噬诱导。此外,我们还提供了证据表明这些过程在人类细胞中是保守的。这些结果进一步阐明了我们对在应激条件下有效诱导自噬所需的转录后机制的理解。