4J7N: Crystal Structure Of Mouse Dxo In Complex With M7gpppg Cap

Citation:
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 1.5A 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.
PDB ID: 4J7NDownload
MMDB ID: 108723
PDB Deposition Date: 2013/2/13
Updated in MMDB: 2014/03
Experimental Method:
x-ray diffraction
Resolution: 1.5  Å
Source Organism:
Similar Structures:
Biological Unit for 4J7N: monomeric; determined by author and by software (PISA)
Molecular Components in 4J7N
Label Count Molecule
Protein (1 molecule)
1
Protein Dom3z(Gene symbol: Dxo)
Molecule annotation
Chemicals (5 molecules)
1
2
2
1
3
2
* Click molecule labels to explore molecular sequence information.

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