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Discovery of a novel type of autophagy targeting RNA
Authors:Yuuki Fujiwara  Akiko Furuta  Hisae Kikuchi  Shu Aizawa  Yusuke Hatanaka  Chiho Konya  Kenko Uchida  Aya Yoshimura  Yoshitaka Tamai  Keiji Wada  Tomohiro Kabuta
Institution: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
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.
Keywords:LAMP  LAMP2  LAMP-2  LAMP2C  LAMP-2C  autophagy  RNA  RNautophagy
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