Lysosomal targeting of SIDT2 via multiple YxxΦ motifs is required for SIDT2 function in the process of RNautophagy
Lysosomal targeting of SIDT2 via multiple YxxΦ motifs is required for SIDT2 function in the process of RNautophagy
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DOI：
10.1242/jcs.202481
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发表时间：
2017-09-01
影响因子：
4
通讯作者：
Kabuta, Tomohiro
中科院分区：
文献类型：
--
作者：
Contu, Viorica Raluca;Hase, Katsunori;Kabuta, Tomohiro
RNA降解是维持细胞稳态的重要过程。在此之前，我们发现了一种新的RNA降解系统，RNautophagy，在此期间，RNA以ATP依赖的方式直接导入溶酶体，然后发生降解。核酸转运蛋白SID-1跨膜家族成员2（SIDT 2）主要定位于溶酶体，并在RNA自噬过程中介导RNA向溶酶体的转运。然而，对SIDT 2分选到溶酶体的机制知之甚少。在这里，我们表明，三个胞质YxxF基序（其中x是任何氨基酸和F是一个氨基酸与庞大的疏水性侧链）是必需的溶酶体定位的SIDT 2，和SIDT 2与adaptorproteincomplexesAP-1和AP-2相互作用。我们还发现，通过这三个基序定位于溶酶体是SIDT 2在RNA自噬过程中发挥功能所必需的，并且SIDT 2在细胞水平上显著增加内源性RNA降解。据我们所知，这是第一个研究报告的内源性细胞内蛋白质的过度表达大大增加细胞内RNA降解。这项研究为蛋白质的溶酶体靶向和细胞内RNA降解提供了新的见解，并进一步证实了SIDT 2在RNA自噬中的关键功能。
RNA degradation is an essential process for maintaining cellular homeostasis. Previously, we 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 acid transporterSID-1 transmembrane family member 2 (SIDT2) predominantly localizes to lysosomes and mediates the translocation ofRNAinto lysosomes duringRNautophagy. However, little is known about the mechanisms of sorting SIDT2 to lysosomes. Here, we showthat three cytosolic YxxFmotifs (inwhich x is any amino acid and F is an amino acid with a bulky hydrophobic side chain) are required for the lysosomal localization of SIDT2, and that SIDT2 interacts with adaptorproteincomplexesAP-1 andAP-2. We also find that localization to lysosomes by these threemotifs is necessary for SIDT2 function in theprocessofRNautophagy, 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 for which overexpression substantially increased 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.