Stability and nuclear localization of yeast telomerase depend on protein components of RNase P/MRP

Garcia, P. Daniela; Leach, Robert W.; Wadsworth, Gable M.; Choudhary, Krishna; Li, Hua; Aviran, Sharon; Kim, Harold D.; Zakian, Virginia A.

doi:10.1038/s41467-020-15875-9

Cited by 30 publications

(36 citation statements)

References 66 publications

(146 reference statements)

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“…3C). Interestingly, also mutations in the Pop-proteins were shown to increase the cytoplasmic presence of TLC1 20 , which supports a model in which loading of the Pop-proteins might occur in the cytoplasm. Thus, in situations, in which TLC1 is not present in the cytoplasm, such as in tlc1∆ or in the export mutant mex67-5 xpo1-1, the Pop-proteins accumulate in the cytoplasm and most likely do not bind TLC1.…”

Section: Mutation Of Cse1 Generates a Type I Like Survivor Phenotypesupporting

confidence: 70%

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Unraveling the stepwise maturation of the yeast telomerase

Becker

Lamping

et al. 2021

Preprint

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Telomerases elongate the ends of chromosomes required for cell immortality through their reverse transcriptase activity. By using the model organism Saccharomyces cerevisiae we defined the order in which the holoenzyme matures. First, a longer precursor of the telomerase RNA, TLC1 is transcribed and exported into the cytoplasm, where it associates with the protecting Sm-ring, the Est- and the Pop-proteins. This partly matured telomerase is re-import into the nucleus via Mtr10 and a novel TLC1-import factor, the karyopherin Cse1. Remarkably, while mutations in all known transport factors result in short telomere ends, mutation in CSE1 bypasses this defect and become Type I like survivors. Interestingly, both import receptors contact the Sm-ring for nuclear import, which therefore resembles a quality control step in the maturation process of the telomerase. The re-imported immature TLC1 is finally trimmed into the ~1150 nucleotide long mature form. TMG-capping of TLC1 finalizes maturation, leading to mature telomerase.

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Section: Mutation Of Cse1 Generates a Type I Like Survivor Phenotypesupporting

confidence: 70%

“…Any way of interfering with the compartmental maturation process inevitably leads to defects in telomere biology (Fig. 5) and 18,20,23,28,30,55,56 , reflecting the importance of this step-wise process.…”

Section: It Was Shown That the Karyopherin Cse1 Contacts The Sm-ring And Particularlymentioning

confidence: 99%

Unraveling the stepwise maturation of the yeast telomerase

Becker

Lamping

et al. 2021

Preprint

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“…RNase MRP proteins Pop1, Pop6, Pop7 are also an essential part of yeast telomerase, where they are involved in the localization of the enzyme and form a structural module that stabilizes the binding of telomerase components Est1 and Est2 28 , 29 .…”

Section: Introductionmentioning

confidence: 99%

Cryo-EM structure of catalytic ribonucleoprotein complex RNase MRP

Perederina

Lee

et al. 2020

Nat Commun

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RNase MRP is an essential eukaryotic ribonucleoprotein complex involved in the maturation of rRNA and the regulation of the cell cycle. RNase MRP is related to the ribozyme-based RNase P, but it has evolved to have distinct cellular roles. We report a cryo-EM structure of the S. cerevisiae RNase MRP holoenzyme solved to 3.0 Å. We describe the structure of this 450 kDa complex, interactions between its components, and the organization of its catalytic RNA. We show that some of the RNase MRP proteins shared with RNase P undergo an unexpected RNA-driven remodeling that allows them to bind to divergent RNAs. Further, we reveal how this RNA-driven protein remodeling, acting together with the introduction of new auxiliary elements, results in the functional diversification of RNase MRP and its progenitor, RNase P, and demonstrate structural underpinnings of the acquisition of new functions by catalytic RNPs.

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“…In addition to fundamental genomic processes, DNA nanotechnology exploits strand displacement to create nanoscale gadgets [12][13][14] and computational circuits [15][16][17][18]. Strand displacement also aids in the development of quantitative assays for detection of nucleic acid [19][20][21] and enzymatic activity [22,23] with improved probe specificity [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

First passage time study of DNA strand displacement

Broadwater

Cook

Kim

2020

Preprint

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6DNA strand displacement, where a single-stranded nucleic acid invades a DNA duplex, is perva-7 sive in genomic processes and DNA engineering applications. The kinetics of strand displacement 8 have been studied in bulk; however, the kinetics of the underlying strand exchange were obfus-9 cated by a slow bimolecular association step. Here, we use a novel single-molecule Fluorescence 10 Resonance Energy Transfer (smFRET) approach termed the "fission" assay to obtain the full dis-11 tribution of first passage times of unimolecular strand displacement. At a frame time of 4.4 ms, 12 the first passage time distribution for a 14-nt displacement domain exhibited a nearly monotonic 13 decay with little delay. Among the eight different sequences we tested, the mean displacement time 14 was on average 35 ms and varied by up to a factor of 13. The measured displacement kinetics also 15 varied between complementary invaders and between RNA and DNA invaders of the same base 16 sequence except for T→U substitution. However, displacement times were largely insensitive to 17 the monovalent salt concentration in the range of 0.25 M to 1 M. Using a one-dimensional random 18 walk model, we infer that the single-step displacement time is in the range of ∼30 µs to ∼300 µs 19 depending on the base identity. The framework presented here is broadly applicable to the kinetic 20 analysis of multistep processes investigated at the single-molecule level. 21 * These two authors contributed equally. † harold.kim@physics.gatech.edu 1 Nucleic acids' ability to form hydrogen bonds between complementary Watson-Crick 2 bases allows for a rich set of complicated, multi-step kinetic behaviors such as duplex 3 hybridization[1] and dehybridization[2], Holliday junction structural dynamics[3, 4], and 4 strand invasion[5]. In particular, strand displacement, which is the exchange of bases 5 between two competing nucleic acid strands of identical sequence, occurs in homologous 6 recombination[6, 7], DNA replication[8] and RNA transcription[9], as well as CRISPR/Cas[10] 7 and the related Cascade complex[11]. In addition to fundamental genomic processes, DNA 8 nanotechnology exploits strand displacement to create nanoscale gadgets[12-14] and com-9 putational circuits[15-18]. Strand displacement also aids in the development of quantitative 10 assays for detection of nucleic acid[19-21] and enzymatic activity[22, 23] with improved 11 probe specificity[24-26]. 12For practical applications, strand displacement is implemented with the "invader" 13 strand and a partial duplex composed of the "incumbent" strand and the "substrate" 14 strand[18] (Fig. 1). The partial duplex has two distinct domains: 1) the single-stranded 15 overhang called the toehold which is critical to the speed and efficiency of the reaction[27] 16 and 2) the duplex region called the displacement domain. Toehold-mediated strand dis-17 placement is initiated when the invader strand anneals to the toehold in a bimolecular 18 reaction. Once a stable toehold interaction is formed, the incumben...

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Stability and nuclear localization of yeast telomerase depend on protein components of RNase P/MRP

Cited by 30 publications

References 66 publications

Unraveling the stepwise maturation of the yeast telomerase

Unraveling the stepwise maturation of the yeast telomerase

Cryo-EM structure of catalytic ribonucleoprotein complex RNase MRP

First passage time study of DNA strand displacement

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