Structure of the Tetrahymena thermophila telomerase RNA helix II template boundary element

Richards, R. J.; Theimer, Carla A.; Finger, L. David; Feigon, Juli

doi:10.1093/nar/gkj481

Cited by 27 publications

(27 citation statements)

References 59 publications

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“…We therefore propose a structural model based on the solved crystal structures of the T. thermophila RBD, the T. castaneum full-length TERT, and NMR structures of stem II of T. thermophila TER which places the base of stem II adjacent to the CP motif (14,15,29) (Fig. 6B).…”

Section: Discussionmentioning

confidence: 99%

A Conserved Motif in Tetrahymena thermophila Telomerase Reverse Transcriptase Is Proximal to the RNA Template and Is Essential for Boundary Definition

Akiyama¹,

Gomez²,

Stone³

2013

Journal of Biological Chemistry

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Background: Telomerase requires the interaction of conserved protein and RNA motifs. Results: Site-directed hydroxyl radical probing and mutagenesis identified an essential region of RNA-protein interactions. Conclusion:The conserved CP2 protein motif is proximal to a conserved telomerase RNA motif. Significance: Understanding how telomerase protein and RNA subunits interact allows us to begin constructing a more complete mechanistic model of telomerase function.

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Section: Discussionmentioning

confidence: 99%

A Conserved Motif in Tetrahymena thermophila Telomerase Reverse Transcriptase Is Proximal to the RNA Template and Is Essential for Boundary Definition

Akiyama¹,

Gomez²,

Stone³

2013

Journal of Biological Chemistry

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“…Immediately 59 of the template sequence is a 5 base-pair (bp) stem with a GNRA tetraloop that could be a template boundary element (TBE), similar to one described for ciliate telomerase RNA (Autexier and Greider 1995). In Tetrahymena, the TBE contains a G-C base pair essential for proper template boundary definition and required for binding of the telomerase core proteintelomerase reverse transcriptase (TERT) (Richards et al 2006), and this G-C pair is present in the Plasmodium RNAs. Potential to form a pseudoknot is a conserved feature of yeast, ciliate, and vertebrate telomerase RNA (Gilley and Blackburn 1999;Chen et al 2000;Dandjinou et al 2004), and disruption of the pseudoknot in ciliates prevents the stable assembly of a catalytically active telomerase in vivo Watson-Crick base apposition to or from a G-U apposition (this is technically not covariation).…”

Section: Telomerase Rnamentioning

confidence: 99%

Structural RNAs of known and unknown function identified in malaria parasites by comparative genomics and RNA analysis

Chakrabarti¹,

Pearson²,

Grate³

et al. 2007

RNA

115

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As the genomes of more eukaryotic pathogens are sequenced, understanding how molecular differences between parasite and host might be exploited to provide new therapies has become a major focus. Central to cell function are RNA-containing complexes involved in gene expression, such as the ribosome, the spliceosome, snoRNAs, RNase P, and telomerase, among others. In this article we identify by comparative genomics and validate by RNA analysis numerous previously unknown structural RNAs encoded by the Plasmodium falciparum genome, including the telomerase RNA, U3, 31 snoRNAs, as well as previously predicted spliceosomal snRNAs, SRP RNA, MRP RNA, and RNAse P RNA. Furthermore, we identify six new RNA coding genes of unknown function. To investigate the relationships of the RNA coding genes to other genomic features in related parasites, we developed a genome browser for P. falciparum (http://areslab.ucsc.edu/cgi-bin/hgGateway). Additional experiments provide evidence supporting the prediction that snoRNAs guide methylation of a specific position on U4 snRNA, as well as predicting an snRNA promoter element particular to Plasmodium sp. These findings should allow detailed structural comparisons between the RNA components of the gene expression machinery of the parasite and its vertebrate hosts.

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“…Distal stem–loop (SL) 4 is the ciliate STE, and is required along with the t/PK for activity. NMR structures of SL2 and SL4 have been determined (22,25,26,39). Stem 4 was crystallized in the presence of telomerase accessory protein p65 C-terminal domain (40).…”

Section: Introductionmentioning

confidence: 99%

Structure and folding of theTetrahymenatelomerase RNA pseudoknot

Cash¹,

Feigon²

2016

Nucleic Acids Res

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Telomerase maintains telomere length at the ends of linear chromosomes using an integral telomerase RNA (TER) and telomerase reverse transcriptase (TERT). An essential part of TER is the template/pseudoknot domain (t/PK) which includes the template, for adding telomeric repeats, template boundary element (TBE), and pseudoknot, enclosed in a circle by stem 1. The Tetrahymena telomerase holoenzyme catalytic core (p65-TER-TERT) was recently modeled in our 9 Å resolution cryo-electron microscopy map by fitting protein and TER domains, including a solution NMR structure of the Tetrahymena pseudoknot. Here, we describe in detail the structure and folding of the isolated pseudoknot, which forms a compact structure with major groove U•A-U and novel C•G-A+ base triples. Base substitutions that disrupt the base triples reduce telomerase activity in vitro. NMR studies also reveal that the pseudoknot does not form in the context of full-length TER in the absence of TERT, due to formation of a competing structure that sequesters pseudoknot residues. The residues around the TBE remain unpaired, potentially providing access by TERT to this high affinity binding site during an early step in TERT-TER assembly. A model for the assembly pathway of the catalytic core is proposed.

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Structure of the Tetrahymena thermophila telomerase RNA helix II template boundary element

Cited by 27 publications

References 59 publications

A Conserved Motif in Tetrahymena thermophila Telomerase Reverse Transcriptase Is Proximal to the RNA Template and Is Essential for Boundary Definition

A Conserved Motif in Tetrahymena thermophila Telomerase Reverse Transcriptase Is Proximal to the RNA Template and Is Essential for Boundary Definition

Structural RNAs of known and unknown function identified in malaria parasites by comparative genomics and RNA analysis

Structure and folding of theTetrahymenatelomerase RNA pseudoknot

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