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Small RNA Modification Sequencing

BS-Seq — Single-Nucleotide tRNA m5C Modification Seq

BS-seq reads 5-methylcytidine (m5C) on tRNA through bisulfite chemistry. Unmodified cytidine is converted and reads as thymine, while m5C is protected and stays cytosine, so every modified site is resolved and quantified at a single nucleotide.

Bisulfite conversion · base-resolution m5C · antibody-free

Overview

Converting cytidine chemistry into an m5C map

On tRNA, m5C reinforces the folded L-shaped structure and fine-tunes anticodon–codon decoding. Bisulfite conversion deaminates unmodified cytidine to uracil, which is read as thymine, while 5-methylcytidine resists the reaction and is read as cytosine, so the conversion pattern itself carries the position information.

Arraystar Single-Nucleotide tRNA m5C Modification Seq(BS-seq) is an end-to-end sample-to-data service for tRNA, from RNA sample QC and tRNA treatment through library construction, sequencing and bioinformatics. Sites are localized within mature tRNA transcripts with relative coordinates, gene attribution, anticodon and isotype, and structural-domain context.

What is tRNA m5C BS-seq?

BS-seq is an antibody-free, base-resolution method for 5-methylcytidine on tRNA. Bisulfite conversion turns unmodified C into U, which reads as T, while m5C is protected and reads as C, so each m5C site is mapped and quantified at single-base resolution.

Service at a Glance

Standard tRNA m5C project — custom designs and add-on analyses available on request

Service NamePrice
Single-Nucleotide tRNA m5C Modification Seq(BS-seq)

Benefits

What bisulfite sequencing delivers for tRNA m5C

Conversion pattern as the read-out

Unmodified cytidine becomes thymine while m5C stays cytosine, so each modified site is separated from the unmodified background base by base.

Fraction from the same signal

The proportion of unconverted reads at a position yields the m5C fraction, which supports quantitative comparison between samples.

No antibody in the workflow

Bisulfite chemistry avoids enrichment bias and cross-reactivity, which is an advantage inside compact and heavily folded tRNA.

Anchored to a mature tRNA

Each call carries relative coordinates, host tRNA gene, anticodon, isotype and structural-domain localization.

Domain-level interpretation

Sites can be grouped by structural domain, so acceptor-stem and loop-region m5C can be compared directly.

Sample-to-data execution

QC, tRNA treatment, library construction, sequencing and bioinformatics are delivered as one project.

Background

m5C, tRNA architecture and decoding

In tRNA the modification stabilises the folded L-shaped structure and fine-tunes anticodon–codon decoding, so base-resolution mapping within maturation loops and the anticodon is what distinguishes one site from another. Position-level data is also what allows m5C to be linked to a specific isotype rather than to a bulk signal (1).

Bisulfite conversion deaminates unmodified cytidine to uracil, read as thymine, while 5-methylcytidine is protected and read as cytosine. Arraystar applies this chemistry in a tRNA workflow and anchors each protected position to the mature transcript and its structural domain (1,2).

tRNA m5C
Figure 1. BS-seq m5C detection scheme. Bisulfite converts unmodified C to U, interpreted as T, while m5C is shielded and reads as C, giving base-resolution m5C quantification.

tRNA m5C BS-Seq Workflow

From total RNA to base-resolution m5C calls

The workflow runs in one line: RNA sample QC with small-RNA-retaining purification, tRNA processing and bisulfite conversion, library construction and sequencing, then conversion-aware alignment and per-site m5C calling.

tRNA m5C BS-Seq Workflow
Figure 2. Single-Nucleotide tRNA m5C Modification Seq workflow.

Bioinformatics & Deliverables

Bioinformatics for tRNA m5C BS-seq

Reads are aligned to a curated tRNA reference, C-to-T conversion signatures are called, and m5C stoichiometry is reported per position together with motif, distribution, differential, enrichment and genome-browser results.

Standard Deliverables

Research Applications

Research directions for tRNA m5C

Anticodon and wobble function

Places m5C inside anticodon and wobble context to test decoding effects.

Structural domain comparison

Compares m5C between the acceptor stem, D-loop, anticodon and TΨC regions.

Isotype-resolved analysis

Contrasts m5C occupancy between tRNA isotypes and isoacceptors.

Writer and eraser studies

Tests how methyltransferase perturbations shift m5C at named positions.

Disease-oriented screening

Identifies differentially methylated tRNA positions between groups.

Sample Requirements

Sample handling and submission for tRNA m5C

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; the amount includes material consumed by sample QC. Questions: support@arraystar.com

FAQ

Questions we are asked about tRNA m5C BS-seq

How does bisulfite chemistry locate an m5C site?
Unmodified cytidine is deaminated to uracil and read as thymine, while 5-methylcytidine resists the reaction and remains cytosine. The unconverted position therefore marks the modified nucleotide itself at single-base resolution, rather than indicating a broadly modified region of the transcript.
How is the modification fraction calculated?
At each cytosine the fraction of reads retaining C rather than converting to T gives the m5C level. Because that fraction is measured per position, sites can be compared quantitatively between samples and conditions without relying on an enrichment step.
Why use an antibody-free route for tRNA?
Enrichment-based methods resolve regions and carry motif bias, and the dense folding of tRNA restricts antibody access. Bisulfite chemistry reports the base directly, so calling does not depend on pull-down efficiency and stoichiometry stays comparable between samples and between batches.
Which tRNA features are annotated?
Sites are reported with relative coordinates inside the mature tRNA transcript, host tRNA gene attribution, anticodon and isotype, and structural-domain localization, so a position can be read within its own tRNA instead of being treated as an unlabelled coordinate on a generic reference.
How much total RNA is required?
At least 10 µg of total RNA per sample, an amount that already accounts for the material consumed by sample QC. RNA should show an OD260/280 ratio of 1.8 or higher with no visible degradation, and twice the minimum is advised to avoid delays.
Can m5C be compared across structural domains?
Yes. Structural-domain localization is attached to every call, so acceptor-stem, D-loop, anticodon and TΨC positions can be grouped and compared rather than being pooled into a single m5C count for the whole tRNA. This makes domain-specific questions answerable from the same dataset.

Selected Publications

Key references for tRNA m5C

  1. Dai Q, Ye C, Irkliyenko I, et al. Ultrafast bisulfite sequencing detection of 5-methylcytosine in DNA and RNA. Nature Biotechnology, 2024. PMID: 38168991
  2. Frommer M, McDonald LE, Millar DS, et al. A genomic sequencing protocol that yields a positive display of 5-methylcytosine residues in individual DNA strands. PNAS, 1992. PMID: 1542678

Read m5C Position by Position in tRNA

Arraystar tRNA m5C BS-seq converts bisulfite chemistry into annotated, quantitative site calls — send us your samples and we will take the project from QC to report.