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Small RNA Modification Sequencing

m1A-Quant-Seq — Single-Nucleotide tRNA m1A Modification Seq

m1A-Quant-seq passes an engineered reverse transcriptase across N1-methyladenosine in tRNA, so each modified position emits a discrete mutation signature. That signature both locates the site and reports its fraction, at single-base resolution and without disturbing the surrounding sequence.

Engineered reverse transcriptase · absolute stoichiometry · antibody-free

Overview

Per-site m1A values inside the tRNA transcriptome

N1-methyladenosine organises the folded tRNA architecture and stabilises codon–anticodon pairing. It sits at conserved positions such as 9, 14 and 58, where it tunes aminoacylation and decoding fidelity, so the useful measurement is the modification level at a named tRNA position rather than a bulk signal.

Arraystar runs m1A-Quant-seq as a complete tRNA project: sample QC, tRNA enrichment, reverse transcription, library preparation, sequencing and tRNA-aware bioinformatics. You receive per-site m1A values with absolute stoichiometry, so the analysis can go straight to the biology instead of stopping at assay assembly.

What is tRNA m1A-Quant-seq?

m1A-Quant-seq is an antibody-free, base-resolution method for N1-methyladenosine on tRNA. An engineered reverse transcriptase reads through m1A and records a reproducible mutation signature at that position; the mutation rate at the site equals the m1A fraction, giving absolute stoichiometry.

Service at a Glance

Standard tRNA m1A project — custom designs and add-on analyses available on request

Service NamePrice
Single-Nucleotide tRNA m1A Modification Seq(m1A-Quant-seq)

Benefits

Why m1A-Quant-seq is used for tRNA

Signatures read through structured tRNA

The engineered enzyme keeps moving through modified, tightly folded tRNA regions instead of stalling before the mark.

Absolute stoichiometry per site

The proportion of mutation signal at a position converts directly into the m1A fraction, which supports quantitative comparison across samples.

Antibody-free by design

No enrichment step means no pull-down bias and no cross-reactivity inside compact tRNA.

Positional context supplied

Every site is mapped within a mature tRNA with anticodon, isodecoder and isotype assignment plus structural-domain context.

Works with limited material

The chemistry tolerates small inputs, which matters when tRNA from primary cells or clinical material is scarce.

Background-controlled calling

A demethylase-treated aliquot provides the baseline against which native signal is scored.

Background

m1A at conserved positions and how it is read

The N1-methyladenosine mark at conserved tRNA positions stabilises the L-shaped fold and fine-tunes aminoacylation and decoding fidelity. Losing or gaining those sites disturbs translation and has been linked to developmental defects and cancer phenotypes, which is why the level at each position is worth measuring (1,2).

Antibody-capture strategies give coarse resolution and struggle with the dense structure of tRNA. m1A-Quant-seq instead relies on reverse transcriptase processivity: as the enzyme crosses the modified base it leaves a reproducible mismatch, and the mutation proportion at that position reports the modification level (1).

tRNA m1A
Figure 1. m1A-Quant-seq scheme for tRNA. The engineered reverse transcriptase reads through N1-methyladenosine and produces a characteristic mutation signature whose rate equals m1A%.

tRNA m1A-Quant-Seq Workflow

From total RNA to per-site m1A stoichiometry

Total RNA is cleared of ribosomal and messenger transcripts, sized into uniform fragments and split into two arms. One arm is demethylated with AlkB as a baseline and the other is left native; both are copied by the engineered enzyme into libraries, sequenced and mapped so that m1A is scored and quantified.

tRNA m1A-Quant-Seq Workflow
Figure 2. m1A-quant-seq workflow for tRNA, from tRNA enrichment and fragmentation through background-controlled reverse transcription to per-site m1A calling.

Bioinformatics & Deliverables

Bioinformatics for m1A-Quant-seq

The tRNA-aware pipeline maps m1A at base resolution, quantifies per-site stoichiometry and flags differential modification. Every site is assigned to the reference tRNA library with anticodon, isodecoder, isotype and structural-domain context, and results arrive as tables, distribution and motif figures and browser-ready tracks.

Standard Deliverables

Research Applications

Where tRNA m1A quantification fits

Translation control

Profiles m1A occupancy on individual tRNAs and compares it with codon-biased translation.

tRNA structure and turnover

Links m1A levels at conserved positions to folding and to tRNA stability.

Cancer and development

Maps m1A changes on the tRNA isotypes that participate in tumour or developmental programmes.

Stress response

Tests whether m1A stoichiometry shifts when cells are challenged.

Isodecoder-level questions

Uses anticodon and isodecoder assignment to separate closely related tRNA genes.

Sample Requirements

Sample handling and submission for tRNA m1A

Sample Storage

  • For cells/tissue: use TRIzol or an RNA-stabilizing reagent, quick-freeze in liquid nitrogen, and keep at –80 °C.
  • For RNA: dissolve in ethanol or RNase-free water, store at –80 °C, and limit freeze–thaw cycles.

Shipping Instructions

  • Transfer each sample into a 1.5 mL nuclease-free tube.
  • Close the tube securely with parafilm or a cap lock to preserve integrity.
  • Send on dry ice with sufficient insulation to sustain the required temperature.
Sample TypeNotes
Whole bloodUse EDTA tubes only; heparin is not compatible with subsequent analytical procedures.
Cultured cellsCell pellets are preferred to ensure high-quality material for processing.
TissueProvide fresh or frozen specimens and avoid necrotic material.
Total RNAMaintain an OD 260/280 ratio ≥ 1.8 and RIN ≥ 7 with no visible degradation. Submit at least 10 µg total RNA.

Submit at least 10 µg total RNA per sample; smaller amounts can be discussed with support@arraystar.com before submission. Questions: support@arraystar.com

FAQ

Questions we are asked about tRNA m1A quantification

How does the assay turn a mutation into an m1A value?
As the engineered reverse transcriptase crosses N1-methyladenosine it introduces a reproducible mismatch at that position. The fraction of reads carrying the mismatch reports the m1A level, so the same signal both locates the site and quantifies it within the tRNA reference.
Why include a demethylated control arm?
The AlkB-treated aliquot removes m1A and therefore shows the background rate of mismatch at the same position. Subtracting that baseline makes the reported stoichiometry attributable to the modification rather than to sequence context, enzyme behaviour or the local structure around the modified base.
Can m1A be assigned to a specific tRNA?
Yes. Every site is mapped within a mature tRNA transcript and carries anticodon, isodecoder, isotype and structural-domain assignment, so a modification level can be read in the context of the tRNA that carries it, including closely related genes within the same isotype family.
How does this compare with antibody-based m1A profiling?
Antibody methods enrich modified fragments and return regional signal, and dense tRNA folding limits antibody access to compact transcripts. m1A-Quant-seq reads through the base itself, giving quantitative site-level values without pull-down bias and without depending on how efficiently an antibody binds its target.
What input amount is realistic?
Around 10 µg of total RNA per sample is the working minimum, and the chemistry tolerates smaller amounts when material is scarce. Purified total RNA is preferred, and RNA extraction from cells, tissue or blood can be arranged before the project starts.
Which biological questions does per-site m1A answer?
Because the read-out is an absolute fraction at a defined tRNA position, it supports questions about codon-biased translation, tRNA turnover under stress and isotype-specific changes in cancer or development, all of which depend on site-level rather than regional modification data.

Selected Publications

Key references for tRNA m1A

  1. Li X, Xiong X, Zhang M, et al. Base-resolution mapping reveals distinct m1A methylome in nuclear- and mitochondrial-encoded transcripts. Molecular Cell, 2017. PMID: 29107537
  2. Wang Y, Zhang J. Clinician's guide to epitranscriptomics: an example of N1-methyladenosine (m1A) RNA modification and cancer. Life, 2024. PMID: 39459530

Quantify m1A Site by Site in Your tRNA Samples

Arraystar tRNA m1A-Quant-seq returns absolute modification levels at named tRNA positions — get in touch and we will scope the project around your sample set.