Lifestyle modifications: coordinating the tRNA epitranscriptome with codon bias to adapt translation during stress responses

Chan, Cheryl; Pham, Phuong; Dedon, Peter C.; Begley, Thomas J.

doi:10.1186/s13059-018-1611-1

Cited by 75 publications

(75 citation statements)

References 82 publications

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“…How translation is regulated in different contexts is of great interest and as tRNAs are central players in decoding genetic information, all forms of regulation over them may have a deep impact in gene expression. Post-transcriptional modification of tRNAs is highly dynamic and adaptable to different situations [49] and has been shown to have deep impact in protein synthesis [38,39,41,50,51]. Understanding the underlying mechanisms that regulate this process, might allow us to manipulate cell behaviors, cell fate or cell death and can have strong impact in cancer treatment [52][53][54] and even be important for establishment of long-term memory [55].…”

Section: Discussionmentioning

confidence: 99%

Elongator Subunit 3 (Elp3) Is Required for Zebrafish Trunk Development

Rojas-Benítez

Allende

2020

IJMS

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Transfer RNAs (tRNAs) are the most post-transcriptionally modified RNA species. Some of these modifications, especially the ones located in the anti-codon loop, are required for decoding capabilities of tRNAs. Such is the case for 5-methoxy-carbonyl-methyl-2-thio-uridine (mcm5s2U), synthetized by the Elongator complex. Mutants for its sub-units display pleiotropic phenotypes. In this paper, we analyze the role of elp3 (Elongator catalytic sub-unit) in zebrafish development. We found that it is required for trunk development; elp3 knock-down animals presented diminished levels of mcm5s2U and sonic hedgehog (Shh) signaling activity. Activation of this pathway was sufficient to revert the phenotype caused by elp3 knockdown, indicating a functional relationship between Elongator and Shh through a yet unknown molecular mechanism.

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Section: Discussionmentioning

confidence: 99%

Elongator Subunit 3 (Elp3) Is Required for Zebrafish Trunk Development

Rojas-Benítez

Allende

2020

IJMS

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“…The cellular activities of each of those enzymes during the maturation of transfer RNAs influence the level of modification of U34 in matured functional tRNAs. Such variations allow to regulate the efficiency of ribosomal translation of particular mRNAs depending on the cellular conditions . The evolution of the genetic code and efficient ribosomal translation is therefore intimately integrated within the biochemical, metabolic, and cellular evolution processes in extant organisms.…”

Section: Discussionmentioning

confidence: 99%

The multiple flavors of GoU pairs in RNA

Westhof

Yusupov

Yusupova

2019

J of Molecular Recognition

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Wobble GU pairs (or GoU) occur frequently within double‐stranded RNA helices interspersed within the standard G═C and A─U Watson‐Crick pairs. However, other types of GoU pairs interacting on their Watson‐Crick edges have been observed. The structural and functional roles of such alternative GoU pairs are surprisingly diverse and reflect the various pairings G and U can form by exploiting all the subtleties of their electronic configurations. Here, the structural characteristics of the GoU pairs are updated following the recent crystallographic structures of functional ribosomal complexes and the development in our understanding of ribosomal translation.

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“…This obviously drives a defined sequential order in the tRNA modification process. In addition, the interdependence of multiple modification events might in certain cases be responsible for the variations of tRNA modifications in response to environmental perturbations (2,7,(15)(16)(17). The characterization of modification circuits is therefore central to understand the dynamic regulation of modifications in tRNAs, however their identification remains difficult since monitoring tRNA maturation at a single nucleotide level in a time-resolved fashion is technically challenging (18).…”

Section: Introductionmentioning

confidence: 99%

Time-resolved NMR monitoring of tRNA maturation

Gato

Heiss

Catala

et al. 2019

Preprint

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Although the biological importance of post-transcriptional RNA modifications in gene expression is widely appreciated, methods to directly detect the introduction of these modifications during RNA biosynthesis are rare and do not easily provide information on the temporal nature of events. Here we introduce the application of NMR spectroscopy to observe the maturation of tRNAs in cell extracts.By following the maturation of yeast tRNA Phe with time-resolved NMR measurements, we found that modifications are introduced in a defined sequential order, and that the chronology is controlled by cross-talk between modification events. In particular, we uncovered a strong hierarchy in the introduction of the T54, Ψ55 and m 1 A58 modifications in the T-arm, and demonstrate that the modification circuits identified in yeast extract with NMR also impact the tRNA modification process in living cells. The NMR-based methodology presented here could be adapted to investigate different aspects of tRNA maturation and RNA modifications in general.

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Lifestyle modifications: coordinating the tRNA epitranscriptome with codon bias to adapt translation during stress responses

Cited by 75 publications

References 82 publications

Elongator Subunit 3 (Elp3) Is Required for Zebrafish Trunk Development

Elongator Subunit 3 (Elp3) Is Required for Zebrafish Trunk Development

The multiple flavors of GoU pairs in RNA

Time-resolved NMR monitoring of tRNA maturation

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