Detection of novel members, structure-function analysis and evolutionary classification of the 2H phosphoesterase superfamily

Abstract

2',3' Cyclic nucleotide phosphodiesterases are enzymes that catalyze at least two distinct steps in the splicing of tRNA introns in eukaryotes. Recently, the biochemistry and structure of these enzymes, from yeast and the plant Arabidopsis thaliana, have been extensively studied. They were found to share a common active site, characterized by two conserved histidines, with the bacterial tRNA-ligating enzyme LigT and the vertebrate myelin-associated 2',3' phosphodiesterases. Using sensitive sequence profile analysis methods, we show that these enzymes define a large superfamily of predicted phosphoesterases with two conserved histidines (hence 2H phosphoesterase superfamily). We identify several new families of 2H phosphoesterases and present a complete evolutionary classification of this superfamily. We also carry out a structure- function analysis of these proteins and present evidence for diverse interactions for different families, within this superfamily, with RNA substrates and protein partners. In particular, we show that eukaryotes contain two ancient families of these proteins that might be involved in RNA processing, transcriptional co-activation and post-transcriptional gene silencing. Another eukaryotic family restricted to vertebrates and insects is combined with UBA and SH3 domains suggesting a role in signal transduction. We detect these phosphoesterase modules in polyproteins of certain retroviruses, rotaviruses and coronaviruses, where they could function in capping and processing of viral RNAs. Furthermore, we present evidence for multiple families of 2H phosphoesterases in bacteria, which might be involved in the processing of small molecules with the 2',3' cyclic phosphoester linkages. The evolutionary analysis suggests that the 2H domain emerged through a duplication of a simple structural unit containing a single catalytic histidine prior to the last common ancestor of all life forms. Initially, this domain appears to have been involved in RNA processing and it appears to have been recruited to perform various other functions in later stages of evolution.

Structure of PhnP, a Phosphodiesterase of the Carbon-Phosphorus Lyase Pathway for Phosphonate Degradation

“…Intriguingly, in 16 operons where phnP was absent, the gene rcsF was present in its stead (the remaining 11 operons contained neither phnP nor rcsF). The rcsF gene product (DUF1045, pfam06299) belongs to the 2H-phosphodiesterase superfamily and is uniquely associated with phn operons (48). This family of phosphodiesterases hydrolyze 2Ј,3Ј-cyclic nucleotides or ribosyl-1Ј,2Ј-cyclic phosphates as part of tRNA splicing reactions and signal transduction.…”

Proteomics and electron microscopic characterization of the unusual mitochondrial ribosome-related 45S complex in Leishmania tarentolae

“…The full domains are present in members of the 2H cyclic phosphodiesterase (CPDase) superfamily which is defined by two Hh[S/T]h (where 'h' is a hydrophobic amino acid) motifs [47]. Only one such unit is present in the LmjF32.0650 protein, however, dimerization of the 45S complexes might bring two units together forming a CPDase active site.…”

Identification of novel components of NAD-utilizing metabolic pathways and prediction of their biochemical functions

“…The presence of a YbiA family NADAR domain in the polyproteins of RNA viruses is also of interest in this regard because it mirrors the earlier reported occurrence of Macro and 2H phosphoesterases (which hydrolyze 2 0 ,3 0 -cyclic phosphates and Appr>p) in diverse RNA and retroviruses. 60,62,63 Thus, it is conceivable that the NADAR domains also perform functions comparable to these enzymes in the above viruses. Finally, the presence of YbiA-like NADAR domains (including phage T4 gp33.3-like proteins) in NCLDVs and several bacteriophages may also be linked to their possession of functionally linked RNA-repair enzymes that include the 2H phosphoesterases and RNA ligases.…”

“…49,97 The archaeoeukaryotic lineage displays several universally conserved RNAprocessing enzymes, such as RNA 2 0 -phosphotransferase (KptA), RNA 3 0 -cyclase, 2H superfamily cyclic phosphodiesterases, and Thg1 polymerases. 63,98,99 In contrast, these are only sporadically distributed in bacteria and may not co-occur as a group in the bacteria that possess them. Hence, it appears likely that these arose first in the archaeo-eukaryotic lineage as View Article Online components of their unique tRNA processing systems, which were subsequently transferred to bacteria and utilized in RNA repair.…”