Open AccessLysosomal targeting of SIDT2 via multiple YXXΦ motifs is required for SIDT2 function in the process of RNautophagy
Author(s) -
Viorica Raluca Contu,
Katsunori Hase,
Hiroko KozukaHata,
Masaaki Oyama,
Yuuki Fujiwara,
Chihana Kabuta,
Masayuki Takahashi,
Fumihiko Hakuno,
Shinichiro Takahashi,
Keiji Wada,
Tomohiro Kabuta
Publication year - 2017
Publication title -
journal of cell science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.384
H-Index - 278
eISSN - 1477-9137
pISSN - 0021-9533
DOI - 10.1242/jcs.202481
Subject(s) - biology , microbiology and biotechnology , rna , intracellular , lysosome , cytosol , rna binding protein , transmembrane protein , protein degradation , biochemistry , gene , enzyme , receptor
RNA degradation is an essential process for maintaining cellular homeostasis. Previously, we have discovered a novel RNA degradation system, RNautophagy, during which direct import of RNA into lysosomes in an ATP-dependent manner followed by degradation takes place. The putative nucleic acids transporter, SID-1 transmembrane family member 2 (SIDT2), predominantly localizes to lysosomes and mediates the translocation of RNA into lysosomes during RNautophagy. However, little is known about the mechanisms of sorting SIDT2 to lysosomes. Here, we showed that three cytosolic YXXΦ motifs are required for the lysosomal localization of SIDT2 and that SIDT2 interacts with adaptor protein complexes AP-1 and AP-2. We also found that localization to lysosomes by these three motifs is necessary for SIDT2 function in the process of RNautophagy, and that SIDT2 strikingly increases endogenous RNA degradation at the cellular level. To our knowledge, this is the first study to report an endogenous intracellular protein of which overexpression substantially boosted intracellular RNA degradation. This study provides new insight into lysosomal targeting of proteins and intracellular RNA degradation, and further confirms the critical function of SIDT2 in RNautophagy.