ATG8 is one of the critical genes that participate in several essential autophagic steps. The expression of ATG8 must be exquisitely regulated to avoid physiological disorder and even cell death. However, the mechanisms of regulating ATG8 expression remain to be fully uncovered. In this investigation, we found that Dicer homologs in Cryptococcus neoformans could activate the expression of ATG8 independent of RNAi. Deletion of two Dicer homologs (DCR1 and DCR2) from C. neoformans, especially DCR2, led to significantly reduced Atg8 protein level, but deletion of other RNAi components did not result in the same phenotype. The autophagic flux, the numbers of autophagic bodies and the tolerance to glucose starvation of dcr2∆ were also significantly reduced. Further investigation showed that Dcr2 activates the expression of ATG8 through the promoter region, not the Open Reading Frame or 3′ Untranslated Region. We also found that a similar phenomenon exists in mammalian cells, as DCR1 instead of AGO2 knockdown also reduced the expression of LC3, indicating that this mechanism may be conservative in eukaryotic cells. Therefore, a novel transcription activation mechanism was revealed in this paper.

中文翻译：

---

Dicer 在新型隐球菌中通过 RNAi 独立机制促进 Atg8 表达

ATG8是参与几个基本自噬步骤的关键基因之一。ATG8的表达必须被精细地调节以避免生理紊乱甚至细胞死亡。然而，调控ATG8表达的机制仍有待完全揭开。在这项调查中，我们发现新生隐球菌中的 Dicer 同源物可以独立于 RNAi激活ATG8的表达。从新型隐球菌，尤其是DCR2 中删除两个 Dicer 同源物（DCR1和DCR2），导致 Atg8 蛋白水平显着降低，但其他 RNAi 成分的缺失不会导致相同的表型。自噬通量、自噬体的数量和dcr2 Δ对葡萄糖饥饿的耐受性也显着降低。进一步的调查表明，DCR2激活的表达ATG8通过启动子区域，而不是开放阅读框或3'非翻译区。我们还发现哺乳动物细胞中也存在类似的现象，因为DCR1而非AGO2敲低也降低了 LC3 的表达，表明这种机制在真核细胞中可能是保守的。因此，本文揭示了一种新的转录激活机制。