Accurate mapping of tRNA reads

Hoffmann, Anne; Fallmann, Jörg; Vilardo, Elisa; Mörl, Mario; Stadler, Peter F.; Amman, Fabian

doi:10.1093/bioinformatics/btx756

Cited by 47 publications

(52 citation statements)

References 59 publications

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“…Trimmed FASTQ files were then mapped using a specific pipeline for tRNAs ( Fig 1A) (Hoffmann et al, 2018). Summarizing, an artificial genome is first generated by masking all annotated tRNA genes and adding pre-tRNAs (i.e., tRNA genes with 3 0 and 5 0 genomic flanking regions) as extra chromosomes.…”

Section: Trna Quantification and Modification Callingmentioning

confidence: 99%

“…Recent technological developments have paved the way for sensitive high-throughput tRNA sequencing across tissues and conditions (Zheng et al, 2015a;Gogakos et al, 2017a). Aside from these methods and despite the lower coverage, tRNA reads can also be detected from generic small RNA-seq datasets (Guo et al, 2015(Guo et al, , 2016Pundhir & Gorodkin, 2015;Torres et al, 2015a;Hoffmann et al, 2018). In this context, The Cancer Genome Atlas (TCGA) has been recently used to investigate the alteration of tRNA gene expression and translational machinery in cancer, which may play a role in driving aberrant translation (Zhang et al, 2018(Zhang et al, , 2019.…”

Section: Introductionmentioning

confidence: 99%

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Translational efficiency across healthy and tumor tissues is proliferation‐related

Hernandez‐Alias

Benisty

Schaefer

et al. 2020

Molecular Systems Biology

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Different tissues express genes with particular codon usage and anticodon tRNA repertoires. However, the codon–anticodon co‐adaptation in humans is not completely understood, nor is its effect on tissue‐specific protein levels. Here, we first validated the accuracy of small RNA‐seq for tRNA quantification across five human cell lines. We then analyzed the tRNA abundance of more than 8,000 tumor samples from TCGA, together with their paired mRNA‐seq and proteomics data, to determine the Supply‐to‐Demand Adaptation. We thereby elucidate that the dynamic adaptation of the tRNA pool is largely related to the proliferative state across tissues. The distribution of such tRNA pools over the whole cellular translatome affects the subsequent translational efficiency, which functionally determines a condition‐specific expression program both in healthy and tumor states. Furthermore, the aberrant translational efficiency of some codons in cancer, exemplified by ProCCA and GlyGGT, is associated with poor patient survival. The regulation of these tRNA profiles is partly explained by the tRNA gene copy numbers and their promoter DNA methylation.

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Section: Trna Quantification and Modification Callingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Translational efficiency across healthy and tumor tissues is proliferation‐related

Hernandez‐Alias

Benisty

Schaefer

et al. 2020

Molecular Systems Biology

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show abstract

“…Quantification of tRNA expression tRNAseq mapping was performed using a specific pipeline for tRNAs (Hoffmann et al, 2018).…”

Section: Computational Analysismentioning

confidence: 99%

Proliferation specific codon usage facilitates oncogene translation

Benisty

Weber

Hernandez‐Alias

et al. 2019

Preprint

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Tumors evolve under selection for gene mutations that give a growth advantage to the cancer cell. Intriguingly, some cancer genes are more often found mutated in tumors than their closely related family members. For example, KRAS mutations are more frequently observed in cancer in comparison to HRAS and NRAS. Here, we find that for RAS and six oncogene families, the most prevalent mutated members in cancer have a codon usage characteristic of genes involved in proliferation. The codon usage of KRAS is more adapted to be efficiently translated in proliferative cells than the codon usage of HRAS. We also show that the translation efficiency of KRAS varies between cell lines in a manner related to their tRNA expression. Altogether, our study demonstrates that a dynamic translation program contributes to shaping the expression profiles of oncogenes. We propose that codon bias related to cell proliferation contributes to the prevalence of mutations in certain members of oncogene families.

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“…All analyses were performed using our tRNAnalysis pipeline (https://github.com/Acribbs/tRNAnalysis). Briefly, all reads passing filter were then subjected to mapping using the human hg38 genome build by using Bowtie1 [ 23] (release 1.2.2) in -v1 alignment mode and best alignment stratum reporting. Initial annotation was performed against all ensemble annotated "small RNAs", "ribosomal RNA" and other RNA annotations.…”

Section: Cell Culture and Protein Synthesis Assaymentioning

confidence: 99%

Maternal circulating syncytiotrophoblast-derived extracellular vesicles contain biologically active 5’-tRNA halves

Cooke

Cribbs

Zhang

et al. 2019

Preprint

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The placenta releases syncytiotrophoblast-derived extracellular vesicles (STB-EV) into the maternal circulation throughout gestation. STB-EV dependent signalling is believed to contribute to the widespread maternal adaptive physiological changes seen in pregnancy.Transfer RNA (tRNA) halves have been identified in vesicles released from other human and murine organ systems, which alter gene expression in target cells. Here, we characterise tRNA-half expression in STB-EV and demonstrate biological activity of a highly abundant tRNA-half. Short RNA from ex-vivo, dual-lobe placental perfusion STB-EV was sequenced,showing that most (>95%) comprised tRNA species. Whole placental tissue contained <50% tRNA species, suggesting selective packaging and export of tRNA into STB-EV. Most tRNA within STB-EV were 5'-tRNA halves cleaved at 30-32 nucleotides. The pattern of tRNA expression differed depending on the size/origin of the STB-EV; this was confirmed by qPCR. Protein synthesis was suppressed in human fibroblasts when they were cultured with a 5'-tRNA half identified from STB-EV sequencing. This study is the first to evaluate tRNA species in STB-EV. The presence of biologically active 5'-tRNA halves, specific to a vesicular origin, suggests a novel mechanism for maternal-fetal signalling in normal pregnancy.

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Accurate mapping of tRNA reads

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 47 publications

References 59 publications

Translational efficiency across healthy and tumor tissues is proliferation‐related

Translational efficiency across healthy and tumor tissues is proliferation‐related

Proliferation specific codon usage facilitates oncogene translation

Maternal circulating syncytiotrophoblast-derived extracellular vesicles contain biologically active 5’-tRNA halves

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