4J7L

Crystal structure of mouse DXO in complex with PRODUCT RNA AND two MAGNESIUM ions

Summary for 4J7L

• Entry DOI: 10.2210/pdb4j7l/pdb
• Related: 3FQI 3FQJ 4J7M 4J7N
• Descriptor: Protein Dom3Z, RNA (5'-R(P*UP*UP*UP*UP*U)-3'), URIDINE 3',5'-BIS(DIHYDROGEN PHOSPHATE), ... (5 entities in total)
• Functional Keywords: decapping, 5'-3' exoribonuclease, hydrolase, hydrolase-rna complex, hydrolase/rna
• Biological source: Mus musculus (mouse); More
• Cellular location: Nucleus (By similarity): O70348
• Total number of polymer chains: 2
• Total formula weight: 45071.17

Authors

Chang, J.H.,Tong, L. (deposition date: 2013-02-13, release date: 2013-03-27, Last modification date: 2024-02-28)

Primary citation

Jiao, X.,Chang, J.H.,Kilic, T.,Tong, L.,Kiledjian, M.
A mammalian pre-mRNA 5' end capping quality control mechanism and an unexpected link of capping to pre-mRNA processing.
Mol.Cell, 50:104-115, 2013

PubMed Abstract: Recently, we reported that two homologous yeast proteins, Rai1 and Dxo1, function in a quality control mechanism to clear cells of incompletely 5' end-capped messenger RNAs (mRNAs). Here, we report that their mammalian homolog, Dom3Z (referred to as DXO), possesses pyrophosphohydrolase, decapping, and 5'-to-3' exoribonuclease activities. Surprisingly, we found that DXO preferentially degrades defectively capped pre-mRNAs in cells. Additional studies show that incompletely capped pre-mRNAs are inefficiently spliced at all introns, a fact that contrasts with current understanding, and are also poorly cleaved for polyadenylation. Crystal structures of DXO in complex with substrate mimic and products at a resolution of up to 1.5Å provide elegant insights into the catalytic mechanism and molecular basis for their three apparently distinct activities. Our data reveal a pre-mRNA 5' end capping quality control mechanism in mammalian cells, indicating DXO as the central player for this mechanism, and demonstrate an unexpected intimate link between proper 5' end capping and subsequent pre-mRNA processing.

PubMed: 23523372
DOI: 10.1016/j.molcel.2013.02.017

Experimental method

X-RAY DIFFRACTION (1.8 Å)