The diverse structural modes of tRNA binding and recognition

Biela, Anna; Hammermeister, Alexander; Kaczmarczyk, Igor; Walczak, Marta; Koziej, L; Lin, Ting‐Yu; Glatt, Sebastian

doi:10.1016/j.jbc.2023.104966

Cited by 13 publications

(11 citation statements)

References 260 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An integral aspect of tRNA structural stability revolves around the strategic positioning of stabilizing modifications, particularly at the junctures between stems called hinge regions. Position 26 and 27, located at the convergence of the D-stem and anticodon stem, alongside positions 44 and 43, situated at the interface of the anticodon and variable arms, serves as a key point of flexibility, facilitating controlled conformational changes essential for tRNA engagement with the ribosome during translation (116). Numerous studies have shown the significant impact of m 2 2G presence within the hinge region on the conformational dynamics of tRNA molecules (24)(25)(26)(27).…”

Section: Discussionmentioning

confidence: 99%

TRMT1L-catalyzed m²₂G27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress

Hwang,

Liao,

Barondeau

et al. 2024

Preprint

View full text Add to dashboard Cite

Mapping of the epitranscriptome has revealed the chemical diversity of RNA modifications and their functional importance in regulating gene expression. Transfer RNAs (tRNAs) are one of the most modified cellular RNAs, containing on average 10-13 modifications per molecule. These modifications have been shown to be critical for several aspects of tRNA functions, such as decoding, folding, and stability. Here we report that the human RNA methyltransferase TRMT1L associates with components of the Rix1 ribosome biogenesis complex and co-sediments with pre-60S ribosomes. Using eCLIP-Seq, we show that TRMT1L binds to a subset of tRNAs and to the 28S rRNA. Additionally, we demonstrate that TRMT1L is responsible for catalyzing N2, N2-dimethylguanosine (m22G) solely at position 27 of tRNA-Tyr-GUA by Nano-tRNAseq and RNA LC-MS. Surprisingly, TRMT1L depletion also impaired the deposition of acp3U and dihydrouridine on tRNA-Tyr-GUA, Cys-GCA, and Ala-CGC. TRMT1L knockout cells have a marked decrease in tRNA-Tyr-GUA levels, coinciding with a reduction in global translation rates and hypersensitivity of oxidative stress. Our results establish TRMT1L as the elusive methyltransferase catalyzing the m22G27 modification on tRNA Tyr, resolving a long-standing gap of knowledge and highlighting its potential role in a tRNA modification circuit crucial for translation regulation and stress response.

show abstract

Section: Discussionmentioning

confidence: 99%

TRMT1L-catalyzed m²₂G27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress

Hwang,

Liao,

Barondeau

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…The higher order structure of tRNA is required for its accommodation in the ribosome during translation. 239 Additionally, proper folding is necessary for recognition and binding by downstream modifying enzymes that recognize tRNAs based on three-dimensional architecture. 240 Many structural modifications occur in the body of the tRNA outside of the anticodon stem-loop, and can block normal base pairing that would collapse the higher-order structure, while simultaneously preserving flexibility and promoting favorable base stacking interactions.…”

Section: Quantitation Of Amino Acid Misincorporation In Living Cellsmentioning

confidence: 99%

“…One of the most prominent roles for tRNA modifications is to ensure pre-tRNA and mature tRNA can assume the correct and stable L-shaped tertiary structure in the cell. The higher order structure of tRNA is required for its accommodation in the ribosome during translation . Additionally, proper folding is necessary for recognition and binding by downstream modifying enzymes that recognize tRNAs based on three-dimensional architecture .…”

Section: Delivery Of Trna Therapeuticsmentioning

confidence: 99%

Mechanisms and Delivery of tRNA Therapeutics

Ward,

Beharry,

Tennakoon

et al. 2024

Chem. Rev.

View full text Add to dashboard Cite

“…The structural core of canonical tRNAs consists of a tight network of tertiary interactions between the D- and T-loops, forming the characteristic “tRNA elbow„ and stabilizing the overall L-shaped fold 21,22 . These conserved structural features serve as recognition sites for enzymes that carry out tRNA maturation and charging 23,24 .…”

Section: Introductionmentioning

confidence: 99%

Molecular basis of human nuclear and mitochondrial tRNA 3’-processing

Bhatta,

Kuhle,

et al. 2024

Preprint

View full text Add to dashboard Cite

Eukaryotic transfer RNA (tRNA) precursors undergo sequential processing steps to become mature tRNAs. In humans, ELAC2 carries out 3 prime-end processing of both nucleus-encoded (nu-tRNAs) and mitochondria-encoded tRNAs (mt-tRNAs). ELAC2 is self-sufficient for processing of nu-tRNAs, but requires TRMT10C and SDR5C1 to process most mt-tRNAs. Here, we show that TRMT10C-SDR5C1 specifically facilitate processing of structurally degenerate mt-tRNAs lacking the canonical elbow. Structures of ELAC2 in complex with TRMT10C, SDR5C1 and two divergent mt-tRNA substrates reveal two distinct mechanisms of pre-tRNA recognition. While canonical nu-tRNAs and mt-tRNAs are recognized by direct ELAC2-RNA interactions, processing of non-canonical mt-tRNAs depends on protein-protein interactions between ELAC2 and TRMT10C. These results provide the molecular basis for tRNA 3 prime-processing in both the nucleus and mitochondria and explain the organelle-specific requirement for additional factors. Moreover, they suggest that TRMT10C-SDR5C1 evolved as a mitochondrial tRNA maturation platform to compensate for the structural erosion of mt-tRNAs in bilaterian animals.

show abstract

The diverse structural modes of tRNA binding and recognition

Cited by 13 publications

References 260 publications

TRMT1L-catalyzed m²₂G27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress

TRMT1L-catalyzed m²₂G27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress

Mechanisms and Delivery of tRNA Therapeutics

Molecular basis of human nuclear and mitochondrial tRNA 3’-processing

Contact Info

Product

Resources

About

The diverse structural modes of tRNA binding and recognition

Cited by 13 publications

References 260 publications

TRMT1L-catalyzed m22G27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress

TRMT1L-catalyzed m22G27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress

Mechanisms and Delivery of tRNA Therapeutics

Molecular basis of human nuclear and mitochondrial tRNA 3’-processing

Contact Info

Product

Resources

About

TRMT1L-catalyzed m²₂G27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress

TRMT1L-catalyzed m²₂G27 on tyrosine tRNA is required for efficient mRNA translation and cell survival under oxidative stress