2. Academic Validation
  3. DXO/Rai1 enzymes remove 5'-end FAD and dephospho-CoA caps on RNAs

DXO/Rai1 enzymes remove 5'-end FAD and dephospho-CoA caps on RNAs

  • Nucleic Acids Res. 2020 Jun 19;48(11):6136-6148. doi: 10.1093/nar/gkaa297.
Selom K Doamekpor 1,  Ewa Grudzien-Nogalska 2,  Agnieszka Mlynarska-Cieslak 3,  Joanna Kowalska 3,  Megerditch Kiledjian 2,  Liang Tong 1
Affiliations

Affiliations

  • 1 Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
  • 2 Dept. Cell Biology and Neuroscience, Rutgers University, Piscataway, NJ 08854, USA.
  • 3 Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, 02-093 Warsaw, Poland.
PMID: 32374864 DOI: 10.1093/nar/gkaa297
Abstract

In 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 ∼200 nucleotides) in human cells and that these RNAs are stabilized in the absence of DXO.

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