Discovery of a novel type of autophagy targeting RNA |
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Authors: | Yuuki Fujiwara Akiko Furuta Hisae Kikuchi Shu Aizawa Yusuke Hatanaka Chiho Konya Kenko Uchida Aya Yoshimura Yoshitaka Tamai Keiji Wada Tomohiro Kabuta |
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Affiliation: | 1.Department of Degenerative Neurological Diseases; National Institute of Neuroscience; National Center of Neurology and Psychiatry; Kodaira, Tokyo Japan;2.Division of Laboratory Animal Resources; National Institute of Neuroscience; National Center of Neurology and Psychiatry; Kodaira, Tokyo Japan;3.Department of Electrical Engineering and Bioscience; Graduate School of Advanced Science and Engineering; Waseda University; Shinjuku, Tokyo Japan |
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Abstract: | Regulated degradation of cellular components by lysosomes is essential to maintain biological homeostasis. In mammals, three forms of autophagy, macroautophagy, microautophagy and chaperone-mediated autophagy (CMA), have been identified. Here, we showed a novel type of autophagy, in which RNA is taken up directly into lysosomes for degradation. This pathway, which we term “RNautophagy,” is ATP-dependent, and unlike CMA, is independent of HSPA8/Hsc70. LAMP2C, a lysosomal membrane protein, serves as a receptor for this pathway. The cytosolic tail of LAMP2C specifically binds to almost all total RNA derived from mouse brain. The cytosolic sequence of LAMP2C and its affinity for RNA are evolutionarily conserved from nematodes to humans. Our findings shed light on the mechanisms underlying RNA homeostasis in higher eukaryotes. |
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Keywords: | LAMP LAMP2 LAMP-2 LAMP2C LAMP-2C autophagy RNA RNautophagy |
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