Mammalian 2′,3′ cyclic nucleotide phosphodiesterase (CNP) can function as a tRNA splicing enzyme in vivo

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Abstract
Yeast and plant tRNA splicing entails discrete healing and sealing steps catalyzed by a tRNA ligase that converts the 2′,3′ cyclic phosphate and 5′-OH termini of the broken tRNA exons to 3′-OH/2′-PO4 and 5′-PO4 ends, respectively, then joins the ends to yield a 2′-PO4, 3′-5′ phosphodiester splice junction. The junction 2′-PO4 is removed by a tRNA phosphotransferase, Tpt1. Animal cells have two potential tRNA repair pathways: a yeast-like system plus a distinctive mechanism, also present in archaea, in which the 2′,3′ cyclic phosphate and 5′-OH termini are ligated directly. Here we report that a mammalian 2′,3′ cyclic nucleotide phosphodiesterase (CNP) can perform the essential 3′ end-healing steps of tRNA splicing in yeast and thereby complement growth of strains bearing lethal or temperature-sensitive mutations in the tRNA ligase 3′ end-healing domain. Although this is the first evidence of an RNA processing function in vivo for the mammalian CNP protein, it seems unlikely that the yeast-like pathway is responsible for animal tRNA splicing, insofar as neither CNP nor Tpt1 is essential in mice.