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Small RNA Modification Sequencing

tRNA Charging Seq — Simultaneous tRNA Expression, Modification & Charging Profiling

tRNA Charging Seq (modification-induced misincorporation tRNA-seq) is a novel and powerful tRNA-seq that can profile tRNA expression, tRNA modifications, and tRNA charging [12]. The method uses a thermostable reverse transcriptase to synthesize full-length cDNA for tRNAs at high efficiency, allowing quantitative analysis of tRNA expression profiles.

One assay · three tRNA profiles · broad modification coverage at single-nucleotide resolution

Overview

One assay for tRNA expression, modification, and charging

As tRNA modifications induce base misincorporations during reverse transcription, tRNA Charging Seq detects the modifications at precise base positions based on the induced mutations in the tRNA sequences. By analyzing 3′-CCA end oxidation/β-elimination, the amino acid charged or uncharged status can be measured.

tRNA Charging Seq overcomes many difficulties of reverse transcription blocks in cDNA synthesis by tRNA modifications and low full-length cDNA yields with old tRNA-seq techniques. It provides tRNA abundance, tRNA modification, and tRNA charging profiles key to tRNA studies in, for example, cancer drug resistance, cardiac fibrosis, and many other diseases.

What is tRNA Charging Seq?

tRNA Charging Seq (modification-induced misincorporation tRNA-seq) is a novel tRNA-seq that profiles tRNA expression, tRNA modifications, and tRNA charging simultaneously. A thermostable reverse transcriptase synthesizes full-length tRNA cDNA at high efficiency; modifications induce base misincorporations that mark their positions, and 3′-CCA end analysis measures amino acid charging.

Service at a Glance

Standard tRNA Charging Seq project — tRNA expression, tRNA modification, and tRNA charging in one assay

Service NameDescriptionPrice
tRNA Charging SeqtRNA expression, tRNA modification, tRNA charging

Benefits

Key advantages of Arraystar tRNA Charging Seq

🧬

Simultaneous tRNA Profiles

tRNA expression, tRNA modification, and tRNA charging are profiled in a single assay.

🚀

High Yields for Full-Length tRNAs

Highly efficient full-length cDNA synthesis to reduce mapping/counting inaccuracy.

🎯

Broad Modification Coverage

tRNA modifications, e.g. m1A, m1G, m3C, acp3U, are predicted at single-nucleotide resolution.

🔗

Translatomics Integration

Correlate tRNA charging with translation activities in the same study.

📊

Rich Data and Analyses

A wealth of tRNA multi-omics data with common analyses (e.g. differential analyses) and detailed annotations.

🖼️

Publication-Ready Graphics

Publication-ready graphics and visualization included in every project.

Background

Why tRNA expression, modification, and charging matter

tRNAs are abundant small RNAs that carry amino acids and decode genetic codons for protein translation in the cells [1]. In addition to the canonical protein translation function, tRNAs have been discovered more recently as active regulators in mRNA translation and diseases by various mechanisms [2-4]. tRNA expression, tRNA modification, and tRNA charging are key profiles in regulating tRNA molecular functions (Fig. 1).

tRNA expression levels profoundly impact mRNA translation. During pathogenesis, changed tRNA repertoires by differential tRNA expression directly regulate the translation efficiency and accuracy of target mRNAs by codon preferences [2]. Cell proliferation, differentiation, and apoptosis are often dynamically regulated by tRNA expression levels.

tRNA modifications exert great influence on protein translation. Certain modifications (e.g. m7G, m1A) can increase the affinity between the tRNA and ribosome to elevate mRNA translation speed and stability, whereas aberrant tRNA modifications can cause ribosome stalling or decoding errors leading to protein synthesis problems [3, 5].

tRNA charging is correlated with mRNA translation efficiency. As only the amino acid charged tRNAs can enter the ribosome and pair with the anticodons, their aminoacylation levels directly determine tRNA translation activities. When tRNA charging is low, translation efficiency is reduced, even enough to touch off mRNA decay, cell malfunction, and pathogenesis [4, 6].

Increasingly, abnormalities in tRNA expression, modification, and charging are linked to cancer [5, 7], cardiovascular [8, 9], neurodegenerative [10], and viral infectious [11] diseases.

Despite their vital importance, profiling tRNA expression, modification, and charging had been technically difficult in the past due to the highly stable tRNA fold structure and heavy tRNA modifications that hinder traditional small RNA sequencing library construction, resulting in poor cDNA yields, biased fragment coverage, and low quantitative accuracy. Arraystar tRNA Charging Seq is the most advanced technology to overcome all the difficulties to simultaneously profile tRNA expression, tRNA modifications, and tRNA charging.

Figure 1. (A) tRNA expression on translation efficiency and mRNA stability. (B) tRNA modification on translation efficiency and mRNA stability. (C) tRNA charging on translation.
Figure 1. (A) tRNA expression on translation efficiency and mRNA stability. (B) tRNA modification on translation efficiency and mRNA stability. (C) tRNA charging on translation.

tRNA Charging Seq Workflow

From total RNA to tRNA expression, modification, and charging profiles

1

Sample QC

RNA quality and quantity assessment before the project proceeds, with small-RNA-retaining purification.

2

cDNA Synthesis

A thermostable reverse transcriptase synthesizes full-length cDNA for tRNAs at high efficiency, overcoming reverse transcription blocks by tRNA modifications.

3

Library Construction & Sequencing

Construction and high-throughput sequencing of the tRNA cDNA library.

4

Modification & Charging Detection

Base misincorporations induced by modifications pinpoint modified positions; 3′-CCA end oxidation/β-elimination analysis measures amino acid charged or uncharged status.

5

Bioinformatics

Differential analyses with detailed annotations for tRNA expression, modification, and charging, with publication-ready graphics and visualization.

Bioinformatics & Deliverables

A wealth of tRNA multi-omics analyses included in every project

tRNA Charging Seq provides a wealth of tRNA multi-omics data with common analyses (e.g. differential analyses) and detailed annotations, for comprehensive insights into the tRNAs. Integrative analyses are also available with other Arraystar services: mRNA-seq, tRF&tiRNA-Seq, Arraystar Small RNA Microarray, and Arraystar Small RNA Modification Microarray.

Standard Deliverables

Figure 2. tRNA differential expression analysis.
Figure 2. tRNA differential expression analysis.
Figure 3. tRNA modification heatmap.
Figure 3. tRNA modification heatmap.
Figure 4. Differential tRNA charging analysis.
Figure 4. Differential tRNA charging analysis.

Research Applications

tRNA multi-omics applications across biology and disease

Cancer Drug Resistance

Valine aminoacyl-tRNA synthetase promotes therapy resistance in melanoma (Nat Cell Biol, 2024); tRNA profiles inform drug resistance and tumor progression studies.

Cardiac Fibrosis

Glutamyl-prolyl-tRNA synthetase regulates proline-rich pro-fibrotic protein synthesis during cardiac fibrosis (Circ Res, 2020).

Cardiovascular Disease

AIMP3 maintains cardiac homeostasis by regulating the editing activity of methionyl-tRNA synthetase (Nat Cardiovasc Res, 2025).

Neurodegenerative Disease

High-fidelity and differential nonsense suppression in live cells and a frontotemporal dementia allele with human transfer RNAs (Nucleic Acids Res, 2025).

Viral Infection

Anticodon engineered transfer RNA inhibits hepatitis B virus replication by promoting degradation of core protein (Adv Sci, 2025).

Translation Regulation

tRNA expression, modification, and charging profiles directly regulate translation efficiency and accuracy by codon preferences, linking to translatomics studies.

Sample Requirements

Official Arraystar sample submission requirements for tRNA Charging Seq

RNA Amount & Quality

  • Total RNA input: > 5 µg per sample (official recommended minimum for the entire experiment in a single attempt, including sample QC). Supply twice the recommended minimum to avoid project delays.
  • Purification: TRIzol / RNA precipitation or an RNA isolation kit. Because tRNA is < 200 nt, use a kit specified to retain small RNAs (e.g. Qiagen miRNeasy).
  • Concentration: > 20 ng/µL by Nanodrop; OD260/280 ~2.0 (acceptable 1.7–2.1); OD260/230 > 1.8.
  • Integrity: sharp 18S/28S rRNA bands by gel, or RIN > 7.0 by Bioanalyzer (serum/plasma/exosome/FFPE RNA exempt).
  • DNase treatment: optional for gDNA removal; required if the sample is also used for qPCR.

Shipping Instructions

  • Ship RNA in nuclease-free water (> 20 ng/µL), freeze-dried, or in ethanol; store at −80 °C or in liquid nitrogen.
  • Use nuclease-free certified, screw-cap 1.5 mL microtubes; seal caps with Parafilm; place tubes in a plastic bag.
  • Use 10 kg dry ice as refrigerant; include a signed Project Form and the sample list.
  • Ship to: Arraystar Inc., 9430 Key West Avenue #128, Rockville, MD 20850, USA. Contact us before shipping.

FAQ

Common questions about tRNA Charging Seq

What profiles does tRNA Charging Seq deliver?
tRNA Charging Seq simultaneously profiles tRNA expression, tRNA modifications, and tRNA charging. tRNA expression is quantified from full-length cDNA; modifications are detected at precise base positions from misincorporations induced during reverse transcription; and amino acid charged or uncharged status is measured by 3′-CCA end oxidation/β-elimination analysis.
How does tRNA Charging Seq overcome the difficulties of traditional tRNA-seq?
Traditional tRNA-seq suffered from highly stable tRNA fold structure and heavy tRNA modifications that block reverse transcription, resulting in poor cDNA yields, biased fragment coverage, and low quantitative accuracy. tRNA Charging Seq uses a thermostable reverse transcriptase to synthesize full-length cDNA at high efficiency, overcoming reverse transcription blocks and reducing mapping/counting inaccuracy.
Which tRNA modifications can be detected?
tRNA Charging Seq offers broad modification coverage; tRNA modifications such as m1A, m1G, m3C, and acp3U are predicted at single-nucleotide resolution based on modification-induced misincorporations during reverse transcription. For modification-specific single-base detection, Arraystar also offers m7G TRAC-Seq, m3C HAC-Seq, and tRNA Modification Seq (m1A, m3C, m1G, m2,2G).
What is the minimum amount of RNA required?
We recommend more than 5 µg of total RNA per sample — the official Arraystar recommended minimum for the entire experiment in a single attempt, including sample QC. Supplying twice the recommended minimum helps avoid project delays. RNA integrity must be preserved, because degraded RNA cannot be rescued by downstream steps.
What bioinformatics analyses are included?
A wealth of tRNA multi-omics data comes with common analyses (e.g. differential analyses) and detailed annotations, including tRNA differential expression analysis, tRNA differential modification analysis, tRNA modification heatmap, and differential tRNA charging analysis. Publication-ready graphics and visualization are delivered with every project.
Can tRNA Charging Seq be combined with other Arraystar services?
Yes. Integrative analyses are available with other Arraystar services, including mRNA-seq, tRF&tiRNA-Seq, Arraystar Small RNA Microarray, and Arraystar Small RNA Modification Microarray. These options support correlating tRNA charging with translation activities and connecting tRNA biology to downstream small RNA profiles in one integrated study.

Selected Publications

Key References for tRNA Charging Seq

  1. Orellana EA, Siegal E, Gregory RI. tRNA dysregulation and disease. Nature Reviews Genetics, 2022. PMID: 35681060
  2. El-Hachem N, et al. Valine aminoacyl-tRNA synthetase promotes therapy resistance in melanoma. Nature Cell Biology, 2024. PMID: 38849541
  3. Dai Z, et al. N(7)-Methylguanosine tRNA modification enhances oncogenic mRNA translation and promotes intrahepatic cholangiocarcinoma progression. Molecular Cell, 2021. PMID: 34352206
  4. Wu J, et al. Glutamyl-Prolyl-tRNA Synthetase Regulates Proline-Rich Pro-Fibrotic Protein Synthesis During Cardiac Fibrosis. Circulation Research, 2020. PMID: 32611237
  5. Qi L, et al. Dual Targeting of m(7)G tRNA Modification and Histone Acetylation using Carrier-Free Nano-Epidrugs to Evoke Osteosarcoma Chemosensitization. Advanced Materials, 2025. PMID: 41074238
  6. Duan Y, et al. A glutamyl-tRNA reductase and its binding protein promote transitory starch biosynthesis and enhance grain quality and yield in rice. Plant Communications, 2025. PMID: 40968536
  7. Qian Y, et al. ALKBH8-mediated codon-specific translation promotes colorectal tumorigenesis. Nature Communications, 2025. PMID: 41083459
  8. Nah J, et al. Microprotein SMIM26 drives oxidative metabolism via serine-responsive mitochondrial translation. Molecular Cell, 2025. PMID: 40578345
  9. Das AS, et al. AIMP3 maintains cardiac homeostasis by regulating the editing activity of methionyl-tRNA synthetase. Nature Cardiovascular Research, 2025. PMID: 40562875
  10. Beharry A, et al. High-fidelity and differential nonsense suppression in live cells and a frontotemporal dementia allele with human transfer RNAs. Nucleic Acids Research, 2025. PMID: 40794874
  11. Yang X, et al. Anticodon Engineered Transfer RNA (tRNA(SUAG)) Inhibits Hepatitis B Virus Replication by Promoting the Degradation of Core Protein. Advanced Science, 2025. PMID: 40940305
  12. Behrens A, Rodschinka G, Nedialkova DD. High-resolution quantitative profiling of tRNA abundance and modification status in eukaryotes by tRNA Charging Seq. Molecular Cell, 2021. PMID: 33581077

Ready to Profile tRNA Expression, Modification & Charging at Once?

Arraystar tRNA Charging Seq delivers tRNA expression, modification, and charging profiles in a single assay — get a quote and a project timeline tailored to your study.