title: Structure and function of echinoderm telomerase RNA.
abstract: Telomerase is a ribonucleoprotein (RNP) enzyme that requires an integral telomerase RNA (TR) subunit, in addition to the catalytic telomerase reverse transcriptase (TERT), for enzymatic function. The secondary structures of TRs from the three major groups of species, ciliates, fungi, and vertebrates, have been studied extensively and demonstrate dramatic diversity. Herein, we report the first comprehensive secondary structure of TR from echinoderms-marine invertebrates closely related to vertebrates-determined by phylogenetic comparative analysis of 16 TR sequences from three separate echinoderm classes. Similar to vertebrate TR, echinoderm TR contains the highly conserved template/pseudoknot and H/ACA domains. However, echinoderm TR lacks the ancestral CR4/5 structural domain found throughout vertebrate and fungal TRs. Instead, echinoderm TR contains a distinct simple helical region, termed eCR4/5, that is functionally equivalent to the CR4/5 domain. The urchin and brittle star eCR4/5 domains bind specifically to their respective TERT proteins and stimulate telomerase activity. Distinct from vertebrate telomerase, the echinoderm TR template/pseudoknot domain with the TERT protein is sufficient to reconstitute significant telomerase activity. This gain-of-function of the echinoderm template/pseudoknot domain for conferring telomerase activity presumably facilitated the rapid structural evolution of the eCR4/5 domain throughout the echinoderm lineage. Additionally, echinoderm TR utilizes the template-adjacent P1.1 helix as a physical template boundary element to prevent nontelomeric DNA synthesis, a mechanism used by ciliate and fungal TRs. Thus, the chimeric and eccentric structural features of echinoderm TR provide unparalleled insights into the rapid evolution of telomerase RNP structure and function.
authors.affiliation: School of Molecular Sciences, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Podlevsky
authors.affiliation: School of Molecular Sciences, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: School of Molecular Sciences, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Julian J-L
authors.initials: JJ
authors.lastname: Chen
mesh_terms: D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D019143:Evolution, Molecular; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012617:Sea Urchins / Q000145:classification / Q000201:enzymology / Q000235:genetics*; D019098:Telomerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D021122:Protein Subunits; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase
keywords: RNA structure; evolution; ribonucleoprotein; telomere; template boundary