期刊
AUTOPHAGY
卷 12, 期 3, 页码 565-578出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2016.1145325
关键词
autophagy; lysosome; membrane protein; RNA; RNautophagy
类别
资金
- Japan Society for the Promotion of Science [24680038, 26111526]
- Ministry of Health, Labor and Welfare, Japan
- Grants-in-Aid for Scientific Research [26860203, 14J08223, 15J06173, 24680038, 26111526, 15J06868] Funding Source: KAKEN
Lysosomes are thought to be the major intracellular compartment for the degradation of macromolecules. We recently identified a novel type of autophagy, RNautophagy, where RNA is directly taken up by lysosomes in an ATP-dependent manner and degraded. However, the mechanism of RNA translocation across the lysosomal membrane and the physiological role of RNautophagy remain unclear. In the present study, we performed gain-and loss-of-function studies with isolated lysosomes, and found that SIDT2 (SID1 transmembrane family, member 2), an ortholog of the Caenorhabditis elegans putative RNA transporter SID-1 (systemic RNA interference deficient-1), mediates RNA translocation during RNautophagy. We also observed that SIDT2 is a transmembrane protein, which predominantly localizes to lysosomes. Strikingly, knockdown of Sidt2 inhibited up to 50% of total RNA degradation at the cellular level, independently of macroautophagy. Moreover, we showed that this impairment is mainly due to inhibition of lysosomal RNA degradation, strongly suggesting that RNautophagy plays a significant role in constitutive cellular RNA degradation. Our results provide a novel insight into the mechanisms of RNA metabolism, intracellular RNA transport, and atypical types of autophagy.
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