tRNA Modifications: Impact on Structure and Thermal Adaptation

Abstract

Transfer RNAs (tRNAs) are central players in translation, functioning as adapter molecules between the informational level of nucleic acids and the functional level of proteins. They show a highly conserved secondary and tertiary structure and the highest density of post-transcriptional modifications among all RNAs. These modifications concentrate in two hotspots—the anticodon loop and the tRNA core region, where the D- and T-loop interact with each other, stabilizing the overall structure of the molecule. These modifications can cause large rearrangements as well as local fine-tuning in the 3D structure of a tRNA. The highly conserved tRNA shape is crucial for the interaction with a variety of proteins and other RNA molecules, but also needs a certain flexibility for a correct interplay. In this context, it was shown that tRNA modifications are important for temperature adaptation in thermophilic as well as psychrophilic organisms, as they modulate rigidity and flexibility of the transcripts, respectively. Here, we give an overview on the impact of modifications on tRNA structure and their importance in thermal adaptation.

The cellular landscape of mid‐size noncoding RNA

“…For example, snRNA modifications, like base methylations, 2′‐O‐methylation, and pseudouridylation, play an important role in spliceosome assembly and regulate splicing efficiency (Bohnsack & Sloan, ; Kiss, ). tRNAs are the most modified RNAs, often by deamination to inosine, various forms of methylation and acetylation (Gogakos et al, ; Lorenz, Lunse, & Morl, ). Modification of tRNA affects folding, stability and function including the decoding of the wobble position and frameshifting (El Yacoubi, Bailly, & de Crecy‐Lagard, ; Lorenz et al, ; Nachtergaele & He, ).…”

RNA stabilization in hyperthermophilic archaea

“…Posttranscriptionally modified nucleosides of tRNAs were shown to modulate their tertiary structure, stability, and coding properties. The tRNA populations of hyperthermophilic archaea were found to be heavily chemically modified, and highly diverse populations of nucleoside modifications were identified via mass spectrometry . Modifications have been mapped for 34 tRNAs of M. jannaschii , revealing several modifications that are unique to archaea and proposed to stabilize the structure of tRNAs or its anticodon–codon interactions .…”

To be or not to be modified: Miscellaneous aspects influencing nucleotide modifications in tRNAs

“…Modified bases in the anticodon‐loop indeed reinforce its U‐turn anticodon‐loop structure. Modifications at positions 32 and especially 37 prevent formations of base pairs between nucleosides 32–38 and 33–37, thereby enabling canonical anticodon‐loop folding .…”