A Structural Basis for Restricted Codon Recognition Mediated by 2-thiocytidine in tRNA Containing a Wobble Position Inosine

Vangaveti, Sweta; Cantara, William A.; Spears, Jessica L.; DeMi̇rci̇, Hasan; Murphy, F.V.; Ranganathan, Sri V.; Sarachan, Kathryn L.; Agris, Paul F.

doi:10.1016/j.jmb.2019.12.016

Cited by 14 publications

(10 citation statements)

References 90 publications

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“…Additionally, it was recently communicated that the I34-A3 base-pair is tightly dependent on the anticodon loop conformation and the modification state of neighboring bases ( Vangaveti et al, 2020 ). Alltogether, these observations highlight the role of base tautomerism in base pairing schemes related to the steric and geometric constraints imposed by the ribosome as originally discussed by Topal & Fresco ( Topal and Fresco, 1976 ).…”

Section: Possible Clues For the Absence Of Trna Genesmentioning

confidence: 99%

On the Track of the Missing tRNA Genes: A Source of Non-Canonical Functions?

Ehrlich

Davyt

López

et al. 2021

Front. Mol. Biosci.

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Cellular tRNAs appear today as a diverse population of informative macromolecules with conserved general elements ensuring essential common functions and different and distinctive features securing specific interactions and activities. Their differential expression and the variety of post-transcriptional modifications they are subject to, lead to the existence of complex repertoires of tRNA populations adjusted to defined cellular states. Despite the tRNA-coding genes redundancy in prokaryote and eukaryote genomes, it is surprising to note the absence of genes coding specific translational-active isoacceptors throughout the phylogeny. Through the analysis of different releases of tRNA databases, this review aims to provide a general summary about those “missing tRNA genes.” This absence refers to both tRNAs that are not encoded in the genome, as well as others that show critical sequence variations that would prevent their activity as canonical translation adaptor molecules. Notably, while a group of genes are universally missing, others are absent in particular kingdoms. Functional information available allows to hypothesize that the exclusion of isodecoding molecules would be linked to: 1) reduce ambiguities of signals that define the specificity of the interactions in which the tRNAs are involved; 2) ensure the adaptation of the translational apparatus to the cellular state; 3) divert particular tRNA variants from ribosomal protein synthesis to other cellular functions. This leads to consider the “missing tRNA genes” as a source of putative non-canonical tRNA functions and to broaden the concept of adapter molecules in ribosomal-dependent protein synthesis.

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Section: Possible Clues For the Absence Of Trna Genesmentioning

confidence: 99%

On the Track of the Missing tRNA Genes: A Source of Non-Canonical Functions?

Ehrlich

Davyt

López

et al. 2021

Front. Mol. Biosci.

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“…Inactivation of ttcA results in hypersensitivity towards hydrogen peroxide and hypochlorite treatments [ 68 ]. TtcA catalyzes the thiolation of C32 on tRNA Arg1 (s 2 C32), a rare modification that restricts codon recognition and improves aminoacylation [ 69 ]. The [4Fe-4S] cluster of TtcA is critical for its function and highly susceptible to damage by ROS.…”

Section: Stress Factors Modulating Trna Modificationsmentioning

confidence: 99%

Extracurricular Functions of tRNA Modifications in Microorganisms

Edwards

Addo

Santos

2020

Genes

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Transfer RNAs (tRNAs) are essential adaptors that mediate translation of the genetic code. These molecules undergo a variety of post-transcriptional modifications, which expand their chemical reactivity while influencing their structure, stability, and functionality. Chemical modifications to tRNA ensure translational competency and promote cellular viability. Hence, the placement and prevalence of tRNA modifications affects the efficiency of aminoacyl tRNA synthetase (aaRS) reactions, interactions with the ribosome, and transient pairing with messenger RNA (mRNA). The synthesis and abundance of tRNA modifications respond directly and indirectly to a range of environmental and nutritional factors involved in the maintenance of metabolic homeostasis. The dynamic landscape of the tRNA epitranscriptome suggests a role for tRNA modifications as markers of cellular status and regulators of translational capacity. This review discusses the non-canonical roles that tRNA modifications play in central metabolic processes and how their levels are modulated in response to a range of cellular demands.

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“…The largest variety and the highest density of nucleobase modifications occur in the ASL domain, which have been suggested to play important roles in maintaining the structural integrity of the anticodon region (Machnicka et al 2014;Schweizer et al 2017). More specifically, some modifications have been proposed to help preorder the structure of the ASL loop to facilitate tRNA accommodation in the ribosome and optimize codonanticodon interactions (Auffinger and Westhof 1999;Sundaram et al 2000;Stuart et al 2003;Agris 2008;Vendeix et al 2008;Denmon et al 2011;Vangaveti et al 2020). The conserved purine at position 37 undergoes a wide assortment of modifications that are phylogenetically distributed among the three domains of life (bacteria, archaea, and eukarya) (Machnicka et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Posttranscriptional modifications at the 37th position in the anticodon stem–loop of tRNA: structural insights from MD simulations

Prabhakar

Takyi

Wetmore

2020

RNA

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Transfer RNA (tRNA) is the most diversely modified RNA. Although the strictly conserved purine position 37 in the anticodon stem–loop undergoes modifications that are phylogenetically distributed, we do not yet fully understand the roles of these modifications. Therefore, molecular dynamics simulations are used to provide molecular-level details for how such modifications impact the structure and function of tRNA. A focus is placed on three hypermodified base families that include the parent i6A, t6A, and yW modifications, as well as derivatives. Our data reveal that the hypermodifications exhibit significant conformational flexibility in tRNA, which can be modulated by additional chemical functionalization. Although the overall structure of the tRNA anticodon stem remains intact regardless of the modification considered, the anticodon loop must rearrange to accommodate the bulky, dynamic hypermodifications, which includes changes in the nucleotide glycosidic and backbone conformations, and enhanced or completely new nucleobase–nucleobase interactions compared to unmodified tRNA or tRNA containing smaller (m1G) modifications at the 37th position. Importantly, the extent of the changes in the anticodon loop is influenced by the addition of small functional groups to parent modifications, implying each substituent can further fine-tune tRNA structure. Although the dominant conformation of the ASL is achieved in different ways for each modification, the molecular features of all modified tRNA drive the ASL domain to adopt the functional open-loop conformation. Importantly, the impact of the hypermodifications is preserved in different sequence contexts. These findings highlight the likely role of regulating mRNA structure and translation.

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A Structural Basis for Restricted Codon Recognition Mediated by 2-thiocytidine in tRNA Containing a Wobble Position Inosine

Cited by 14 publications

References 90 publications

On the Track of the Missing tRNA Genes: A Source of Non-Canonical Functions?

On the Track of the Missing tRNA Genes: A Source of Non-Canonical Functions?

Extracurricular Functions of tRNA Modifications in Microorganisms

Posttranscriptional modifications at the 37th position in the anticodon stem–loop of tRNA: structural insights from MD simulations

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