title: Discovery of a novel type of autophagy targeting RNA.
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.
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Akiko
authors.initials: A
authors.lastname: Furuta
authors.forename: Hisae
authors.initials: H
authors.lastname: Kikuchi
authors.forename: Shu
authors.initials: S
authors.lastname: Aizawa
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Hatanaka
authors.forename: Chiho
authors.initials: C
authors.lastname: Konya
authors.forename: Kenko
authors.initials: K
authors.lastname: Uchida
authors.forename: Aya
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tamai
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kabuta
mesh_terms: D000818:Animals; D001343:Autophagy; D001921:Brain / Q000196:embryology / Q000378:metabolism; D017124:Conserved Sequence; D006367:HeLa Cells; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2 / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D012313:RNA / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D052119:Lysosomal-Associated Membrane Protein 2; D012313:RNA
keywords: LAMP; LAMP-2; LAMP-2C; LAMP2; LAMP2C; RNA; RNautophagy; autophagy