Evolution of Telomerase RNA
abstract: The highly specialized telomerase ribonucleoprotein enzyme is composed minimally of telomerase reverse transcriptase (TERT) and telomerase RNA (TR) for catalytic activity. Telomerase is an RNA-dependent DNA polymerase that syntheizes DNA repeats at chromosome ends to maintain genome stabil...
Other Authors: | |
---|---|
Format: | Doctoral Thesis |
Language: | English |
Published: |
2019
|
Subjects: | |
Online Access: | http://hdl.handle.net/2286/R.I.55597 |
id |
ndltd-asu.edu-item-55597 |
---|---|
record_format |
oai_dc |
spelling |
ndltd-asu.edu-item-555972020-01-15T03:01:11Z Evolution of Telomerase RNA abstract: The highly specialized telomerase ribonucleoprotein enzyme is composed minimally of telomerase reverse transcriptase (TERT) and telomerase RNA (TR) for catalytic activity. Telomerase is an RNA-dependent DNA polymerase that syntheizes DNA repeats at chromosome ends to maintain genome stability. While TERT is highly conserved among various groups of species, the TR subunit exhibits remarkable divergence in primary sequence, length, secondary structure and biogenesis, making TR identification extremely challenging even among closely related groups of organisms. A unique computational approach combined with in vitro telomerase activity reconstitution studies was used to identify 83 novel TRs from 10 animal kingdom phyla spanning 18 diverse classes from the most basal sponges to the late evolving vertebrates. This revealed that three structural domains, pseudoknot, a distal stem-loop moiety and box H/ACA, are conserved within TRs from basal groups to vertebrates, while group-specific elements emerge or disappear during animal TR evolution along different lineages. Next the corn-smut fungus Ustilago maydis TR was identified using an RNA-immunoprecipitation and next-generation sequencing approach followed by computational identification of TRs from 19 additional class Ustilaginomycetes fungi, leveraging conserved gene synteny among TR genes. Phylogenetic comparative analysis, in vitro telomerase activity and TR mutagenesis studies reveal a secondary structure of TRs from higher fungi, which is also conserved with vertebrates and filamentous fungi, providing a crucial link in TR evolution within the opisthokonta super-kingdom. Lastly, work by collabarotors from Texas A&M university and others identified the first bona fide TR from the model plant Arabidopsis thaliana. Computational analysis was performed to identify 85 novel AtTR orthologs from three major plant clades: angiosperms, gymnosperms and lycophytes, which facilitated phylogenetic comparative analysis to infer the first plant TR secondary structural model. This model was confirmed using site-specific mutagenesis and telomerase activity assays of in vitro reconstituted enzyme. The structures of plant TRs are conserved across land plants providing an evolutionary bridge that unites the disparate structures of previously characterized TRs from ciliates and vertebrates. Dissertation/Thesis Logeswaran, Dhenugen (Author) Chen, Julian J-L (Advisor) Ghirlanda, Giovanna (Committee member) Borges, Chad R (Committee member) Arizona State University (Publisher) Biochemistry Molecular biology Bioinformatics Basidiomycota Metazoa Plant Telomerase Telomerase RNA eng 188 pages Doctoral Dissertation Biochemistry 2019 Doctoral Dissertation http://hdl.handle.net/2286/R.I.55597 http://rightsstatements.org/vocab/InC/1.0/ 2019 |
collection |
NDLTD |
language |
English |
format |
Doctoral Thesis |
sources |
NDLTD |
topic |
Biochemistry Molecular biology Bioinformatics Basidiomycota Metazoa Plant Telomerase Telomerase RNA |
spellingShingle |
Biochemistry Molecular biology Bioinformatics Basidiomycota Metazoa Plant Telomerase Telomerase RNA Evolution of Telomerase RNA |
description |
abstract: The highly specialized telomerase ribonucleoprotein enzyme is composed minimally of telomerase reverse transcriptase (TERT) and telomerase RNA (TR) for catalytic activity. Telomerase is an RNA-dependent DNA polymerase that syntheizes DNA repeats at chromosome ends to maintain genome stability. While TERT is highly conserved among various groups of species, the TR subunit exhibits remarkable divergence in primary sequence, length, secondary structure and biogenesis, making TR identification extremely challenging even among closely related groups of organisms.
A unique computational approach combined with in vitro telomerase activity reconstitution studies was used to identify 83 novel TRs from 10 animal kingdom phyla spanning 18 diverse classes from the most basal sponges to the late evolving vertebrates. This revealed that three structural domains, pseudoknot, a distal stem-loop moiety and box H/ACA, are conserved within TRs from basal groups to vertebrates, while group-specific elements emerge or disappear during animal TR evolution along different lineages.
Next the corn-smut fungus Ustilago maydis TR was identified using an RNA-immunoprecipitation and next-generation sequencing approach followed by computational identification of TRs from 19 additional class Ustilaginomycetes fungi, leveraging conserved gene synteny among TR genes. Phylogenetic comparative analysis, in vitro telomerase activity and TR mutagenesis studies reveal a secondary structure of TRs from higher fungi, which is also conserved with vertebrates and filamentous fungi, providing a crucial link in TR evolution within the opisthokonta super-kingdom.
Lastly, work by collabarotors from Texas A&M university and others identified the first bona fide TR from the model plant Arabidopsis thaliana. Computational analysis was performed to identify 85 novel AtTR orthologs from three major plant clades: angiosperms, gymnosperms and lycophytes, which facilitated phylogenetic comparative analysis to infer the first plant TR secondary structural model. This model was confirmed using site-specific mutagenesis and telomerase activity assays of in vitro reconstituted enzyme. The structures of plant TRs are conserved across land plants providing an evolutionary bridge that unites the disparate structures of previously characterized TRs from ciliates and vertebrates. === Dissertation/Thesis === Doctoral Dissertation Biochemistry 2019 |
author2 |
Logeswaran, Dhenugen (Author) |
author_facet |
Logeswaran, Dhenugen (Author) |
title |
Evolution of Telomerase RNA |
title_short |
Evolution of Telomerase RNA |
title_full |
Evolution of Telomerase RNA |
title_fullStr |
Evolution of Telomerase RNA |
title_full_unstemmed |
Evolution of Telomerase RNA |
title_sort |
evolution of telomerase rna |
publishDate |
2019 |
url |
http://hdl.handle.net/2286/R.I.55597 |
_version_ |
1719308525725810688 |