RNautophagy/DNautophagy possesses selectivity for RNA/DNA substrates.
RNautophagy/DNautophagy possesses selectivity for RNA/DNA substrates.
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DOI：
10.1093/nar/gkv579
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发表时间：
2015-07-27
影响因子：
14.9
通讯作者：
Kabuta T
中科院分区：
文献类型：
--
作者：
Hase K;Fujiwara Y;Kikuchi H;Aizawa S;Hakuno F;Takahashi S;Wada K;Kabuta T
溶酶体可以降解各种生物大分子，包括核酸、蛋白质和脂质。最近，我们确定了新的核酸降解系统称为RNautophagy/DNautophagy（缩写为RDA），其中RNA和DNA直接被溶酶体以ATP依赖的方式吸收并降解。我们还发现，溶酶体膜蛋白，LAMP 2C，其细胞质区域结合到RNA和DNA，功能，至少部分，作为RNA/DNA受体在RDA的过程中。然而，目前还不清楚RDA是否具有对RNA/DNA底物的选择性，并且尚未确定LAMP 2C识别的RNA/DNA序列。在本研究中，我们发现LAMP 2C的胞质区域与poly-G/dG结合，但不与poly-A/dA、poly-C/dC、poly-dT或poly-U结合。与这种结合活性一致，poly-G/dG通过RDA转运到分离的溶酶体中，而poly-A/dA、poly-C/dC、poly-dT和poly-U则没有。GGGGGG或d（GGGG）序列对于poly-G/dG和LAMP 2C之间的相互作用是必需的。除了聚-G/dG，富含G/dG的序列，如重复的GGGGCC序列，与LAMP 2C的胞质区域相互作用。我们的研究结果表明RDA确实对RNA/DNA底物具有选择性，并且至少一些连续的G/dG序列可以介导RDA。
Lysosomes can degrade various biological macromolecules, including nucleic acids, proteins and lipids. Recently, we identified novel nucleic acid-degradation systems termed RNautophagy/DNautophagy (abbreviated as RDA), in which RNA and DNA are directly taken up by lysosomes in an ATP-dependent manner and degraded. We also found that a lysosomal membrane protein, LAMP2C, the cytoplasmic region of which binds to RNA and DNA, functions, at least in part, as an RNA/DNA receptor in the process of RDA. However, it has been unclear whether RDA possesses selectivity for RNA/DNA substrates and the RNA/DNA sequences that are recognized by LAMP2C have not been determined. In the present study, we found that the cytosolic region of LAMP2C binds to poly-G/dG, but not to poly-A/dA, poly-C/dC, poly-dT or poly-U. Consistent with this binding activity, poly-G/dG was transported into isolated lysosomes via RDA, while poly-A/dA, poly-C/dC, poly-dT and poly-U were not. GGGGGG or d(GGGG) sequences are essential for the interaction between poly-G/dG and LAMP2C. In addition to poly-G/dG, G/dG-rich sequences, such as a repeated GGGGCC sequence, interacted with the cytosolic region of LAMP2C. Our findings indicate that RDA does possess selectivity for RNA/DNA substrates and that at least some consecutive G/dG sequence(s) can mediate RDA.