Alignment-free discovery of conserved RNA structures in the human genome
- 1Faculty of Science and Engineering, Waseda University
Abstract
Many functional RNAs were first found as conserved RNA structures, and their roles in gene regulation were identified later. In humans and other vertebrates, imperfect genome alignments have hindered the discovery of such structures. Here we present RLMHelix, which selects candidate conserved RNA structures from single sequences before any alignment by scoring helices supported by language-model dependencies and thermodynamics. Through distillation, RLMHelix rapidly scans the transcribed human genome and ranks known RNAs higher than conventional thermodynamic scanning. Two-thirds of 15,821 candidates are new to four earlier genome-wide screens, yet agree with in-cell probing, and over half retain structural signal in homologues. In eCLIP data and in exploratory pull-downs, higher RLMHelix scores were associated with more binding by double-stranded RNA-binding proteins. By linking candidates to their binding proteins, RLMHelix yields testable functional hypotheses and illuminates a path from unrecognized human RNA structures to RNA biology and therapeutic targets.
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BibTeX
@misc{sumi2026alignmentfree,
title = {{Alignment-free discovery of conserved RNA structures in the human genome}},
author = {S. Sumi and K. Makino and M. Onoguchi and S. Adachi and H. Saito and M. Hamada},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.24.761493},
url = {https://www.biorxiv.org/content/10.64898/2026.10.24.761493v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Alignment-free discovery of conserved RNA structures in the human genome
AU - S. Sumi
AU - K. Makino
AU - M. Onoguchi
AU - S. Adachi
AU - H. Saito
AU - M. Hamada
PY - 2026
DA - 2026/10/24
PB - bioRxiv
DO - 10.64898/2026.10.24.761493
UR - https://www.biorxiv.org/content/10.64898/2026.10.24.761493v1
AB - Many functional RNAs were first found as conserved RNA structures, and their roles in gene regulation were identified later. In humans and other vertebrates, imperfect genome alignments have hindered the discovery of such structures. Here we present RLMHelix, which selects candidate conserved RNA structures from single sequences before any alignment by scoring helices supported by language-model dependencies and thermodynamics. Through distillation, RLMHelix rapidly scans the transcribed human genome and ranks known RNAs higher than conventional thermodynamic scanning. Two-thirds of 15,821 candidates are new to four earlier genome-wide screens, yet agree with in-cell probing, and over half retain structural signal in homologues. In eCLIP data and in exploratory pull-downs, higher RLMHelix scores were associated with more binding by double-stranded RNA-binding proteins. By linking candidates to their binding proteins, RLMHelix yields testable functional hypotheses and illuminates a path from unrecognized human RNA structures to RNA biology and therapeutic targets.
ER -