Anticodon stem-loop tRNA modifications influence codon decoding and frame maintenance during translation

Smith, T.J.; Giles, Rachel; Koutmou, Kristin S.

doi:10.1016/j.semcdb.2023.06.003

Cited by 14 publications

(5 citation statements)

References 127 publications

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“…The rest of the tRNAs harbour A37, which is modified most frequently to ms 2 i 6 A, m 6 t 6 A, i 6 A, t 6 A, m 6 A and m 2 A. Threonylcarbamoyladenosine-type (t 6 A, m 6 t 6 A) and isopentyladenosinetype (i 6 A, ms 2 i 6 A) modifications enhance base-stacking to stabilise the codon-anticodon interactions. They also maintain the open structure of the anticodon loop by weakening U33-A37 pairing (Figure 4a, b; (90,91)). Although our method was insufficient for the detection of most known A37 modifications, it showed the presence of a prokaryotic-type modificationms 2 i 6 A in most annotated E. coli tRNAs (Figure 2a-c, Supplementary Table 2).…”

Section: The Context Of Chloroplast Trna Modificationsmentioning

confidence: 98%

Deciphering the RNA Modification Landscape in Arabidopsis Chloroplast tRNAs and rRNAs Reveals a Blend of Ancestral and Acquired Characteristics

Gołębiewska,

Gregorová,

Sarin

et al. 2024

Preprint

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Chloroplasts in plant leaves are essential for protein synthesis, relying on transfer RNAs (tRNAs) and ribosomal RNAs (rRNAs) encoded by the chloroplast genome. Although post-transcriptional modifications of these non-coding RNAs are common in many systems, chloroplast tRNA and rRNA modifications are not well characterised.In this study, we investigated the post-transcriptional modifications in chloroplast tRNAs and rRNAs ofArabidopsis thalianausing tRNA sequencing, liquid chromatography-mass spectrometry, targeted rRNA sequencing, and analysis of public data.Our results revealed similarities between chloroplast non-coding RNAs and bacterial systems (e.g.,Escherichia coli), such as modification patterns at the anticodon-adjacent position and the variable loop of tRNAs, along with conserved modifications in the small subunit rRNA. Additionally, we identified features shared with eukaryotic systems that likely contribute to the correct three-dimensional structure of chloroplast tRNAs. Unique modifications were also discovered, including a potential novel modification at wobble position in tRNA-IleCAU, which may be crucial for distinguishing isoleucine codons from methionine codons, and chloroplast-specific rRNA modifications that likely compensate for altered ribosome structure.These findings suggest that the chloroplast translation machinery, through co-evolution with its eukaryotic host, has adopted features beyond those typically found in bacteria, reflecting a blend of ancestral and acquired characteristics.

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Section: The Context Of Chloroplast Trna Modificationsmentioning

confidence: 98%

Deciphering the RNA Modification Landscape in Arabidopsis Chloroplast tRNAs and rRNAs Reveals a Blend of Ancestral and Acquired Characteristics

Gołębiewska,

Gregorová,

Sarin

et al. 2024

Preprint

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“…The post-transcriptional modification of transfer RNA (tRNA) has emerged as a critical modulator of biological processes ranging from gene expression to development 1,2 . In particular, tRNA modifications play critical roles in tRNA structure, stability, and function in protein synthesis 3-5 . Defects in tRNA modification have emerged as the cause for many types of human diseases, highlighting the critical role of tRNA modification in human health and physiology 6-8 .…”

Section: Main Textmentioning

confidence: 99%

Epileptic encephalopathy linked to a DALRD3 missense variant impaired in tRNA modification function

Zhang,

Löhner,

Lemmink

et al. 2024

Preprint

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Epileptic encephalopathies are severe epilepsy syndromes characterized by early onset and progressive cerebral dysfunction. A nonsense variant in the DALR Anticodon Binding Domain Containing 3 (DALRD3) gene has been implicated in epileptic encephalopathy but no other disease-associated variants in DALRD3 have been described. In human cells, the DALRD3 protein forms a complex with the METTL2 methyltransferase to generate the 3-methylcytosine (m3C) modification in specific arginine tRNAs. Here, we identify a patient with a homozygous missense variant in DALRD3 who displays developmental delay, cognitive deficiencies, and multifocal epilepsy. The missense variant substitutes an arginine residue to cysteine (R517C) within the DALR domain of DALRD3 that is required for binding tRNAs. Patient cells homozygous for the DALRD3-R517C variant exhibit reduced levels of m3C modification in arginine tRNAs, indicating that the R517C variant impairs DALRD3 function. Notably, the DALRD3-R517C variant displays reduced association with METTL2 and loss of interaction with substrate tRNAs. Our results uncover a novel pathogenic variant in DALRD3 that links DALRD3 loss-of-function to epileptic encephalopathy disorders. Importantly, these findings underscore DALRD3-dependent tRNA modification as a key contributor to proper brain development and function.

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“…tRNAs are frequently post-transcriptionally imbued with diverse modifications that drastically impact their structure and function ( Lorenz et al, 2017 ; Suzuki, 2021 ; Cappannini et al, 2024 ; Yared et al, 2024 ). tRNAs exhibit diverse modifications in all arms, but they are most frequent at the tRNA core and anticodon arm ( Cantara et al, 2011 ; Smith et al, 2024 ). Anticodon arm modifications in particular have thus been targets for uncovering tRNA translation fidelity principles as an “unrealized genetic code” to complement the tRNA sequence itself ( Agris et al, 2017 ).…”

Section: Improving Codon-anticodon Interactionsmentioning

confidence: 99%

Tuning tRNAs for improved translation

Weiss,

Decker,

Bolano

et al. 2024

Front. Genet.

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Transfer RNAs have been extensively explored as the molecules that translate the genetic code into proteins. At this interface of genetics and biochemistry, tRNAs direct the efficiency of every major step of translation by interacting with a multitude of binding partners. However, due to the variability of tRNA sequences and the abundance of diverse post-transcriptional modifications, a guidebook linking tRNA sequences to specific translational outcomes has yet to be elucidated. Here, we review substantial efforts that have collectively uncovered tRNA engineering principles that can be used as a guide for the tuning of translation fidelity. These principles have allowed for the development of basic research, expansion of the genetic code with non-canonical amino acids, and tRNA therapeutics.

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Anticodon stem-loop tRNA modifications influence codon decoding and frame maintenance during translation

Cited by 14 publications

References 127 publications

Deciphering the RNA Modification Landscape in Arabidopsis Chloroplast tRNAs and rRNAs Reveals a Blend of Ancestral and Acquired Characteristics

Deciphering the RNA Modification Landscape in Arabidopsis Chloroplast tRNAs and rRNAs Reveals a Blend of Ancestral and Acquired Characteristics

Epileptic encephalopathy linked to a DALRD3 missense variant impaired in tRNA modification function

Tuning tRNAs for improved translation

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