Bulk RNA degradation by nitrogen starvation-induced autophagy in yeast

Bulk RNA degradation by nitrogen starvation-induced autophagy in yeast
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DOI:
10.15252/embj.201489083
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发表时间:
2015-01-14
期刊:
影响因子:
11.4
通讯作者:
Fukusaki, Eiichiro
Fukusaki, Eiichiro
中科院分区:
生物学1区
文献类型:
--
作者:
Huang, Hanghang;Kawamata, Tomoko;Fukusaki, Eiichiro

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自噬是真核生物中保守的分解代谢过程。在营养饥饿的情况下,一部分细胞质非选择性地被隔离到自噬体中。因此,核糖体被递送到空泡/溶酶体进行破坏,但自噬RNA降解的精确机制及其对细胞代谢的生理意义仍然未知。我们在酵母中使用代谢组学和分子生物学分析的组合表征了自噬依赖的RNA催化剂。递送到液泡的RNA由T2型核糖核酸酶Rny 1处理,产生3-NMPs,3-NMPs立即被液泡非特异性磷酸酶Pho 8转化为核苷。在细胞质中,这些核苷被核苷酶Pmp 1和Urh 1分解。大多数生成的碱基没有被重新同化,而是从细胞中排出。大量非选择性自噬引起代谢的剧烈扰动,必须将其最小化以维持细胞内稳态。
Autophagy is a catabolic process conserved among eukaryotes. Under nutrient starvation, a portion of the cytoplasm is non-selectively sequestered into autophagosomes. Consequently, ribosomes are delivered to the vacuole/lysosome for destruction, but the precise mechanism of autophagic RNA degradation and its physiological implications for cellular metabolism remain unknown. We characterized autophagy-dependent RNA catabolism using a combination of metabolome and molecular biological analyses in yeast. RNA delivered to the vacuole was processed by Rny1, a T2-type ribonuclease, generating 3-NMPs that were immediately converted to nucleosides by the vacuolar non-specific phosphatase Pho8. In the cytoplasm, these nucleosides were broken down by the nucleosidases Pnp1 and Urh1. Most of the resultant bases were not re-assimilated, but excreted from the cell. Bulk non-selective autophagy causes drastic perturbation of metabolism, which must be minimized to maintain intracellular homeostasis.