Prevalent and distinct spliceosomal 3′-end processing mechanisms for fungal telomerase RNA

Qi, Xiaodong; Rand, Dustin P.; Podlevsky, Joshua D.; Li, Yang; Mosig, Axel; Stadler, Peter F.; Chen, Julian J.‐L.

doi:10.1038/ncomms7105

Cited by 24 publications

(26 citation statements)

References 35 publications

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“…Despite broad conservation of activity-critical TERT domains and TER motifs that co-fold to form the enzyme catalytic core, entirely different pathways of telomerase biogenesis and regulation have evolved in ciliates, fungi, and vertebrates (32, 45). Even within fungi, a remarkable extent of divergence has occurred in the telomerase RNP assembly and telomere recruitment pathways (85, 86). In this section, we focus on telomerase cellular requirements and regulations that can be compared across species.…”

Section: Cellular Ribonucleoprotein Assembly and Action At Telomeresmentioning

confidence: 99%

“…The TER precursor 3′ end is determined in S. cerevisiae by the Nrd1/Nab3/Sen1 transcription termination pathway (92), in most other fungi by intentionally aborted splicing (85, 86, 93), and in human cells by transcription-coupled cleavage and polyadenylation machinery (94). Proteins protect a mature TER 3′ end by blocking exonuclease access.…”

Section: Cellular Ribonucleoprotein Assembly and Action At Telomeresmentioning

confidence: 99%

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Telomerase Mechanism of Telomere Synthesis

Upton

Vogan

et al. 2017

Annu. Rev. Biochem.

193

186

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Telomerase is the essential reverse transcriptase required for linear chromosome maintenance in most eukaryotes. Telomerase supplements the tandem array of simple-sequence repeats at chromosome ends to compensate for the DNA erosion inherent in genome replication. The template for telomerase reverse transcriptase is within the RNA subunit of the ribonucleoprotein complex, which in cells contains additional telomerase holoenzyme proteins that assemble the active ribonucleoprotein and promote its function at telomeres. Telomerase is distinct among polymerases in its reiterative reuse of an internal template. The template is precisely defined, processively copied, and regenerated by release of single-stranded product DNA. New specificities of nucleic acid handling that underlie the catalytic cycle of repeat synthesis derive from both active site specialization and new motif elaborations in protein and RNA subunits. Studies of telomerase provide unique insights into cellular requirements for genome stability, tissue renewal, and tumorigenesis as well as new perspectives on dynamic ribonucleoprotein machines.

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Section: Cellular Ribonucleoprotein Assembly and Action At Telomeresmentioning

confidence: 99%

Section: Cellular Ribonucleoprotein Assembly and Action At Telomeresmentioning

confidence: 99%

Telomerase Mechanism of Telomere Synthesis

Upton

Vogan

et al. 2017

Annu. Rev. Biochem.

193

186

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“…The TERs of Pezizomycotina and Taphrinomycotina share core features of vertebrate TERs. In particular, they have a fairly well-conserved secondary structure of the pseudoknot and the TWJ,and at least in these regions the sequence is sufficiently conserved for successful homology-based identification of TERs within these clades [22–24]. The TERs known for Saccharomycetes, the relatives of budding yeast, on the other hand, are sometimes remarkably large and present little similarity in sequence and secondary structure to vertebrate or ciliate TERs.…”

Section: Introductionmentioning

confidence: 99%

TERribly Difficult: Searching for Telomerase RNAs in Saccharomycetes

Waldl

Thiel

Ochsenreiter

et al. 2018

Preprint

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The telomerase RNA in yeasts is large, usually > 1, 000 nt, and contains functional elements 1 that have been extensively studied experimentally in several disparate species. Nevertheless, they 2 are very difficult to detect by homology-based methods and so far have escaped annotation in the 3 majority of the genomes of Saccharomycotina. This is a consequence of sequences that evolve rapidly 4 at nucleotide level, are subject to large variations in size, and are highly plastic with respect to 5 their secondary structures. Here we report on a survey that was aimed at closing this gap in RNA 6 annotation. Despite considerable efforts and the combination of a variety of different methods, it 7 was only partially successful. While 27 new telomerase RNAs were identified, we had to restrict our 8 efforts to the subgroup Saccharomycetacea because even this narrow subgroup was diverse enough to 9 require different search models for different phylogenetic subgroups. More distant branches of the 10 Saccharomycotina still remain without annotated telomerase RNA. 11

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“…Ciliate TRs are transcribed by RNA polymerase (pol) III and contain a terminal poly(U) tract that is common for small RNAs (17), while vertebrate and fungal TRs are transcribed by RNA pol II with nascent poly(A) tails that are removed by 3′-end processing with the exception of budding yeast RNA pol II transcription termination by the Nrd1-Nab3-Sen1 pathway (18–24). The recently identified TR from the flagellated protozoan Trypanosoma brucei was found to be approximately one kilobase-pair in length, transcribed by RNA pol II, and the nascent transcript trans spliced with a spliced leader RNA common for trypanosome mRNAs (25,26).…”

Section: Introductionmentioning

confidence: 99%

The functional requirement of two structural domains within telomerase RNA emerged early in eukaryotes

Podlevsky¹,

Li²,

Chen³

2016

Nucleic Acids Res

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Telomerase emerged during evolution as a prominent solution to the eukaryotic linear chromosome end-replication problem. Telomerase minimally comprises the catalytic telomerase reverse transcriptase (TERT) and telomerase RNA (TR) that provides the template for telomeric DNA synthesis. While the TERT protein is well-conserved across taxa, TR is highly divergent amongst distinct groups of species. Herein, we have identified the essential functional domains of TR from the basal eukaryotic species Trypanosoma brucei, revealing the ancestry of TR comprising two distinct structural core domains that can assemble in trans with TERT and reconstitute active telomerase enzyme in vitro. The upstream essential domain of T. brucei TR, termed the template core, constitutes three short helices in addition to the 11-nt template. Interestingly, the trypanosome template core domain lacks the ubiquitous pseudoknot found in all known TRs, suggesting later evolution of this critical structural element. The template-distal domain is a short stem-loop, termed equivalent CR4/5 (eCR4/5). While functionally similar to vertebrate and fungal CR4/5, trypanosome eCR4/5 is structurally distinctive, lacking the essential P6.1 stem-loop. Our functional study of trypanosome TR core domains suggests that the functional requirement of two discrete structural domains is a common feature of TRs and emerged early in telomerase evolution.

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Prevalent and distinct spliceosomal 3′-end processing mechanisms for fungal telomerase RNA

Cited by 24 publications

References 35 publications

Telomerase Mechanism of Telomere Synthesis

Telomerase Mechanism of Telomere Synthesis

TERribly Difficult: Searching for Telomerase RNAs in Saccharomycetes

The functional requirement of two structural domains within telomerase RNA emerged early in eukaryotes

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