Molecular mechanism of human ISG20L2 for the ITS1 cleavage in the processing of 18S precursor ribosomal RNA

Yinliang Ma1; Jiaxu Wang1,2; Xingyi He1; Yuhang Liu1; Shuo Zhen1; Lina An1; Qian Yang1; Fumin Niu1; Hong Wang1; Boran An3; Xinyue Tai1; Zhenzhen Yan1; Chen Wu1; Xiaoyun Yang1,4; Xiuhua Liu1

2023-12-28

10.1093/nar/gkad1210

Nucleic Acids Research   影响因子和分区

0305-1048

1362-4962

["The exonuclease ISG20L2 has been initially characterized for its role in the mammalian 5.8S rRNA 3 ' end maturation, specifically in the cleavage of ITS2 of 12S precursor ribosomal RNA (pre-rRNA). Here, we show that human ISG20L2 is also involved in 18S pre-rRNA maturation through removing the ITS1 region, and contributes to ribosomal biogenesis and cell proliferation. Furthermore, we determined the crystal structure of the ISG20L2 nuclease domain at 2.9 angstrom resolution. It exhibits the typical alpha beta alpha fold of the DEDD 3 '-5 ' exonuclease with a catalytic pocket located in the hollow near the center. The catalytic residues Asp183, Glu185, Asp267, His322 and Asp327 constitute the DEDDh motif in ISG20L2. The active pocket represents conformational flexibility in the absence of an RNA substrate. Using structural superposition and mutagenesis assay, we mapped RNA substrate binding residues in ISG20L2. Finally, cellular assays revealed that ISG20L2 is aberrantly up-regulated in colon adenocarcinoma and promotes colon cancer cell proliferation through regulating ribosome biogenesis. Together, these results reveal that ISG20L2 is a new enzymatic member for 18S pre-rRNA maturation, provide insights into the mechanism of ISG20L2 underlying pre-rRNA processing, and suggest that ISG20L2 is a potential therapeutic target for colon adenocarcinoma.","[GRAPHICS]"]

SCI

英语

通讯

National Natural Science Foundation of China["32171295","32071277"] ; National Natural Science Foundation of China["C2022201025","C2020201030"] ; Natural Science Foundation of Hebei province[ZD2020183] ; Hebei Educational committee Foundation["DXK202006","DXK202007"] ; Interdisciplinary Research Program of Natural Science of Hebei University[C20200303]

Biochemistry & Molecular Biology

Biochemistry & Molecular Biology

WOS:001132598200001

OXFORD UNIV PRESS

BIOLOGY & BIOCHEMISTRY

人工提交

正式出版

1.College of Life Sciences, Hebei Innovation Center for Bioengineering and Biotechnology, Institute of Life Sciences and Green Development, Hebei University, Baoding 071002 Hebei, China
2.College of Life Sciences, State Key Laboratory of Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Normal University, Xinxiang 453002 Henan, China
3.Affiliated Hospital of Hebei University, Hebei University, Baoding 071002 Hebei, China
4.Department of Biology, Southern University of Science and Technology, Shenzhen 518055 Guangdong, China

Yinliang Ma,Jiaxu Wang,Xingyi He,et al. Molecular mechanism of human ISG20L2 for the ITS1 cleavage in the processing of 18S precursor ribosomal RNA[J]. Nucleic Acids Research,2023,52(4).

Yinliang Ma.,Jiaxu Wang.,Xingyi He.,Yuhang Liu.,Shuo Zhen.,...&Xiuhua Liu.(2023).Molecular mechanism of human ISG20L2 for the ITS1 cleavage in the processing of 18S precursor ribosomal RNA.Nucleic Acids Research,52(4).

Yinliang Ma,et al."Molecular mechanism of human ISG20L2 for the ITS1 cleavage in the processing of 18S precursor ribosomal RNA".Nucleic Acids Research 52.4(2023).