Although the function of tRNAs in the translational process is well established, it remains controversial whether tRNA abundance is tightly associated with translational efficiency (TE) in mammals. Moreover, how critically the expression of tRNAs contributes to the establishment of tissue-specific proteomes in mammals has not been well addressed. Here, we measured both tRNA expression using demethylase-tRNA sequencing (DM-tRNA-seq) and TE of mRNAs using ribosome-tagging sequencing (RiboTag-seq) in the brain, heart, and testis of mice. Remarkable variation in the expression of tRNA isodecoders was observed among different tissues. When the statistical effect of isodecoder-grouping on reducing variations is considered through permutating the anticodons, we observed an expected reduction in the variation of anticodon expression across all samples, an unexpected smaller variation of anticodon usage bias, and an unexpected larger variation of tRNA isotype expression at amino acid level. Regardless of whether or not they share the same anticodons, the isodecoders encoding the same amino acids are co-expressed across different tissues. Based on the expression of tRNAs and the TE of mRNAs, we find that the tRNA adaptation index (tAI) and TE are significantly correlated in the same tissues but not between tissues; and tRNA expression and the amino acid composition of translating peptides are positively correlated in the same tissues but not between tissues. We therefore hypothesize that the tissue-specific expression of tRNAs might be due to post-transcriptional mechanisms. This study provides a resource for tRNA and translation studies, as well as novel insights into the dynamics of tRNAs and their roles in translational regulation.
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http://dx.doi.org/10.1016/j.gpb.2022.07.006 | DOI Listing |
Nat Struct Mol Biol
January 2025
Laboratory of Regulation of Gene Expression, Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic.
Transfer RNAs (tRNAs) serve as a dictionary for the ribosome translating the genetic message from mRNA into a polypeptide chain. In addition to this canonical role, tRNAs are involved in other processes such as programmed stop codon readthrough (SC-RT). There, tRNAs with near-cognate anticodons to stop codons must outcompete release factors and incorporate into the ribosomal decoding center to prevent termination and allow translation to continue.
View Article and Find Full Text PDFActa Crystallogr F Struct Biol Commun
February 2025
Graduate School of Life Science, Hokkaido University, Kita 10, Nishi 8, Kita-ku, Sapporo, Hokkaido 060-0810, Japan.
The bacterial enzyme tRNA 2-selenouridine synthase (SelU) catalyzes the conversion of 5-substituted 2-thiouridine (R5S2U) to 5-substituted 2-selenouridine (R5Se2U) at the wobble positions of several tRNAs. Seleno-modification potentially regulates translation efficiency in response to selenium availability. Notably, SelU uses the 2-geranylthiouridine (R5geS2U) intermediate for sulfur removal, and this geranylthiol (geS) is a unique leaving group among tRNA-maturation enzymes.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China.
Thiolation, a post-transcriptional modification catalyzed by Uba4-Urm1-Ncs2/Ncs6 pathway in three specific transfer RNAs (tRNAs), is conserved from yeast to humans and plays an important role in enhancing codon-anticodon interaction and translation efficiency. Yet, except for affecting effector secretion, its roles in plant pathogenic fungi are not fully understood. Here, we used Magnaporthe oryzae as a model system to illustrate the vital role of s2U34 modification on the appressorium-mediated virulence.
View Article and Find Full Text PDFNucleic Acids Res
January 2025
Division of Pharmacoengineering and Molecular Pharmaceutics, The University of North Carolina at Chapel Hill, 125 Mason Farm Rd. Chapel Hill, NC 27599, USA.
Whole genome codon compression-the reassignment of all instances of a specific codon to synonymous codons-can generate organisms capable of tolerating knockout of otherwise essential transfer RNAs (tRNAs). As a result, such knockout strains enable numerous unique applications, such as high-efficiency production of DNA encoding extremely toxic genes or non-canonical proteins. However, achieving stringent control over protein expression in these organisms remains challenging, particularly with proteins where incomplete repression results in deleterious phenotypes.
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