In silico identification and structural characterization of telomerase reverse transcriptases in parasitic...

Telomere shortening during eukaryotic cell division can lead to severe problems such as inactivation of neighboring genes and aberrant chromosomal fusion. To protect chromosome ends from the replicative errors, most eukaryotes have evolved an enzymatic defense mechanism called telomerase, in which telomerase reverse transcriptase (TERT) plays a central role. This enzymatic activity is highly elevated in consecutively dividing somatic cells of regenerating and probably asexually reproducing, platyhelminths. Therefore, flatworms can be powerful models to investigate the biological implications of TERT in these non-embryonic developments. Current information on the protein is largely limited to a handful of representative species within the phylum Platyhelminthes. This study characterizes the structural features of TERT proteins and their encoding genes in flatworms, aiming to expand our knowledge of the telomere-protecting protein in this lower animal taxon. The platyhelminth genes exhibited exon-intron architectures that were highly divergent from their orthologs in the other lophotrochozoans, and their protein products lacked some TERT-specific domains such as the telomerase essential N-terminal and repeat addition processivity domains. Nevertheless, the unique gene and protein structures were tightly conserved among the flatworm homologs. Analysis of the tert transcripts showed that use of alternative splice acceptors or donors in a minor AT-AC intron, as well as intron retention and exon exclusion, contribute to the generation of aberrant mRNAs. The present findings demonstrate that the tert gene has undergone structural changes soon after the emergence of the platyhelminth lineage, which might have been coordinated with those of its functional counterpart, the telomerase RNA molecule.