ANGEL2 is a member of the CCR4 family of deadenylases with 2',3'-cyclic phosphatase activity

Science. 2020 Jul 31;369(6503):524-530. doi: 10.1126/science.aba9763.


RNA molecules are frequently modified with a terminal 2',3'-cyclic phosphate group as a result of endonuclease cleavage, exonuclease trimming, or de novo synthesis. During pre-transfer RNA (tRNA) and unconventional messenger RNA (mRNA) splicing, 2',3'-cyclic phosphates are substrates of the tRNA ligase complex, and their removal is critical for recycling of tRNAs upon ribosome stalling. We identified the predicted deadenylase angel homolog 2 (ANGEL2) as a human phosphatase that converts 2',3'-cyclic phosphates into 2',3'-OH nucleotides. We analyzed ANGEL2's substrate preference, structure, and reaction mechanism. Perturbing ANGEL2 expression affected the efficiency of pre-tRNA processing, X-box-binding protein 1 (XBP1) mRNA splicing during the unfolded protein response, and tRNA nucleotidyltransferase 1 (TRNT1)-mediated CCA addition onto tRNAs. Our results indicate that ANGEL2 is involved in RNA pathways that rely on the ligation or hydrolysis of 2',3'-cyclic phosphates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Exoribonucleases / chemistry*
  • Exoribonucleases / genetics
  • Gene Knockout Techniques
  • HEK293 Cells
  • Humans
  • Nucleotidases / chemistry*
  • Nucleotidases / genetics
  • Protein Structure, Secondary
  • RNA Precursors
  • RNA Splicing
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Ribonucleases / chemistry*
  • Ribonucleases / genetics
  • Substrate Specificity
  • X-Box Binding Protein 1 / genetics


  • RNA Precursors
  • RNA, Messenger
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • ANGEL2 protein, human
  • Exoribonucleases
  • Ribonucleases
  • Nucleotidases
  • 3'-nucleotidase