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The Pat1-Lsm complex prevents 3′ to 5′ degradation of a specific subset of ATG mRNAs during nitrogen starvation-induced autophagy

机译:Pat1-Lsm复合物可防止氮饥饿诱导的自噬过程中ATG mRNA特定子集的3至5降解

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摘要

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 transcripts. In a recent study we showed that, during nitrogen starvation, the RNA-binding complex Pat1-Lsm is involved in binding and preventing the 3ʹ to 5ʹ exosome-mediated degradation of a specific subset of mRNAs. Dephosphorylation of Pat1 at residues S456 and S457 facilitates mRNA binding, resulting in 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.
机译:宏观自噬/自噬(一种保守的分解代谢循环途径)的失调与多种疾病的发生和发展有关。虽然自噬相关蛋白(Atg)的翻译后调控一直是重要的研究重点,导致在理解自噬调控方面取得重大突破,但对转录本的转录后调控了解甚少。在最近的研究中,我们表明,在氮饥饿期间,RNA结合复合物Pat1-Lsm参与结合并阻止3ʹ至5ʹ外来体介导的特定mRNA降解。在残基S456和S457上Pat1的去磷酸化促进了mRNA的结合,导致mRNA积累,Atg蛋白合成和强大的自噬诱导作用。另外,我们提供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的转录后机制的理解。

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