6wuk
From Proteopedia
Crystal structure of mouse DXO in complex with CoA
Structural highlights
FunctionDXO_MOUSE Ribonuclease that specifically degrades pre-mRNAs with a defective 5' end cap and is part of a pre-mRNA capping quality control. Has decapping, pyrophosphohydrolase and 5'-3' exonuclease activities. Has decapping activity toward incomplete 5' end cap mRNAs such as unmethylated 5' end-capped RNA to release GpppN and 5' end monophosphate RNA. The 5' end monophosphate RNA is then degraded by the 5'-3' exoribonuclease activity, enabling this enzyme to decap and degrade incompletely capped mRNAs. Also possesses RNA 5'-pyrophosphohydrolase activity by hydrolyzing the 5' end triphosphate to release pyrophosphates.[1] Publication Abstract from PubMedIn eukaryotes, the DXO/Rai1 enzymes can eliminate most of the incomplete and non-canonical NAD caps through their decapping, deNADding and pyrophosphohydrolase activities. Here, we report that these enzymes can also remove FAD and dephospho-CoA (dpCoA) non-canonical caps from RNA, and we have named these activities deFADding and deCoAping. The crystal structures of mammalian DXO with 3'-FADP or CoA and fission yeast Rai1 with 3'-FADP provide elegant insight to these activities. FAD and CoA are accommodated in the DXO/Rai1 active site by adopting folded conformations. The flavin of FAD and the pantetheine group of CoA contact the same region at the bottom of the active site tunnel, which undergoes conformational changes to accommodate the different cap moieties. We have developed FAD-capQ to detect and quantify FAD-capped RNAs and determined that FAD caps are present on short RNAs (with less than approximately 200 nucleotides) in human cells and that these RNAs are stabilized in the absence of DXO. DXO/Rai1 enzymes remove 5'-end FAD and dephospho-CoA caps on RNAs.,Doamekpor SK, Grudzien-Nogalska E, Mlynarska-Cieslak A, Kowalska J, Kiledjian M, Tong L Nucleic Acids Res. 2020 May 6. pii: 5831185. doi: 10.1093/nar/gkaa297. PMID:32374864[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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