Oral Presentation Australasian RNA Biology and Biotechnology Association 2025 Conference

Decoding the (epi)transcriptome at single-molecule resolution (127701)

Eduardo Eyras 1
  1. AUSTRALIAN NATIONAL UNIVERSITY, Canberra, ACT, Australia

Messenger RNAs (mRNAs) carry the genetic instructions that cells use to produce proteins that are essential for life. Beyond their basic sequence, mRNAs are chemically modified in ways that can influence their stability, translation, and function, collectively known as the epitranscriptome. These modifications are increasingly linked to diseases such as cancer and neurodegeneration, yet their full landscape and biological roles remain poorly understood. To address this gap, we have developed advanced computational tools that detect and map RNA modifications across the transcriptome at single-molecule resolution. By training on controlled datasets and known cellular modification sites, these tools analyse ionic signals from nanopore sequencing devices to identify modified nucleotides with high accuracy. Applying these models across diverse species and conditions, we uncover conserved patterns of RNA modifications and demonstrate that these marks are deposited early during transcription, well before splicing occurs. Our findings challenge existing assumptions and open new avenues for understanding how RNA modifications regulate gene expression. Our tools offer a powerful framework for mapping the epitranscriptome across diverse biological contexts, providing new insights into RNA biology and disease mechanisms.