7YW5

Crystal Structure of the ITS1 processing by human ribonuclease ISG20L2 with mutation D327A

Summary for 7YW5

• Entry DOI: 10.2210/pdb7yw5/pdb
• Descriptor: Interferon-stimulated 20 kDa exonuclease-like 2 (2 entities in total)
• Functional Keywords: ribonuclease, ribosomal protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 43568.19

Authors

Yang, X.Y.,Liu, X.H. (deposition date: 2022-08-21, release date: 2024-01-17, Last modification date: 2024-03-13)

Primary citation

Ma, Y.,Wang, J.,He, X.,Liu, Y.,Zhen, S.,An, L.,Yang, Q.,Niu, F.,Wang, H.,An, B.,Tai, X.,Yan, Z.,Wu, C.,Yang, X.,Liu, X.
Molecular mechanism of human ISG20L2 for the ITS1 cleavage in the processing of 18S precursor ribosomal RNA.
Nucleic Acids Res., 52:1878-1895, 2024

PubMed Abstract: 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 Å resolution. It exhibits the typical αβα 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.

PubMed: 38153123
DOI: 10.1093/nar/gkad1210

Experimental method

X-RAY DIFFRACTION (2.77 Å)