LAUSR

Deadenylating RNA molecules Transfer RNA (tRNA) and messenger RNA molecules often acquire a terminal 2′,3′-cyclic phosphate group when processed in the cell. These cyclic phosphates provide attachment points for tRNA ligases and must be removed to recycle tRNAs from stalled ribosomes. Pinto et al. identified a deadenylase from human tissue culture cells that can do the job. Biochemical characterization and analysis of a crystal structure reveal ANGEL2 as a 2′,3′-cyclic phosphatase with functions for RNA processing and modification. Science, this issue p. 524 The RNA phosphatase ANGEL2 affects transfer RNA processing and unconventional messenger RNA splicing in human cells. 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.