title: Lysosomal putative RNA transporter SIDT2 mediates direct uptake of RNA by lysosomes.
abstract: 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.
authors.affiliation: a Department of Degenerative Neurological Diseases , National Institute of Neuroscience, National Center of Neurology and Psychiatry , Kodaira , Tokyo , Japan.
authors.forename: Shu
authors.initials: S
authors.lastname: Aizawa
authors.affiliation: a Department of Degenerative Neurological Diseases , National Institute of Neuroscience, National Center of Neurology and Psychiatry , Kodaira , Tokyo , Japan.|b Department of Electrical Engineering and Bioscience , Graduate School of Advanced Science and Engineering, Waseda University , Shinjuku-ku , Tokyo , Japan.
authors.forename: Yuuki
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: a Department of Degenerative Neurological Diseases , National Institute of Neuroscience, National Center of Neurology and Psychiatry , Kodaira , Tokyo , Japan.|c Department of Neurology , Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi , Chuo , Yamanashi , Japan.
authors.forename: Viorica Raluca
authors.initials: VR
authors.lastname: Contu
authors.affiliation: a Department of Degenerative Neurological Diseases , National Institute of Neuroscience, National Center of Neurology and Psychiatry , Kodaira , Tokyo , Japan.|b Department of Electrical Engineering and Bioscience , Graduate School of Advanced Science and Engineering, Waseda University , Shinjuku-ku , Tokyo , Japan.
authors.forename: Katsunori
authors.initials: K
authors.lastname: Hase
authors.affiliation: a Department of Degenerative Neurological Diseases , National Institute of Neuroscience, National Center of Neurology and Psychiatry , Kodaira , Tokyo , Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: a Department of Degenerative Neurological Diseases , National Institute of Neuroscience, National Center of Neurology and Psychiatry , Kodaira , Tokyo , Japan.
authors.forename: Hisae
authors.initials: H
authors.lastname: Kikuchi
authors.affiliation: a Department of Degenerative Neurological Diseases , National Institute of Neuroscience, National Center of Neurology and Psychiatry , Kodaira , Tokyo , Japan.
authors.forename: Chihana
authors.initials: C
authors.lastname: Kabuta
authors.affiliation: a Department of Degenerative Neurological Diseases , National Institute of Neuroscience, National Center of Neurology and Psychiatry , Kodaira , Tokyo , Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.affiliation: a Department of Degenerative Neurological Diseases , National Institute of Neuroscience, National Center of Neurology and Psychiatry , Kodaira , Tokyo , Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kabuta
mesh_terms: D000818:Animals; D001343:Autophagy; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D052119:Lysosomal-Associated Membrane Protein 2 / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D033704:Nucleotide Transport Proteins / Q000378:metabolism*; D011485:Protein Binding; D012313:RNA / Q000378:metabolism*; D020871:RNA Stability; D034443:RNA Transport
chemical_list: D052119:Lysosomal-Associated Membrane Protein 2; D008565:Membrane Proteins; D033704:Nucleotide Transport Proteins; C000613088:SIDT2 protein, human; C554947:Sidt2 protein, mouse; D012313:RNA
keywords: RNA; RNautophagy; autophagy; lysosome; membrane protein