Document Type
Article
Publication Date
10-13-2025
Abstract
We report that in humans, mice, fruit flies, and worms, the ribosomal RNAs and the transcribed spacers of 45S are densely packed with organism-specific sequence motifs that are primarily shared with nervous system genes. The human ribosomal RNAs and 45S spacers contain 1,723 such motifs. Specific combinations of these motifs are predominantly found in 3,430 human nervous system genes, of which 1,046 are genes associated with brain disorders, including autism spectrum disorder and schizophrenia. The sequences of the 1,723 motifs and their locations in the introns and exons of nervous system genes are unique to primates. Experimental evidence indicates that the motifs are contact points for ribosomal-RNA|messenger-RNA and messenger-RNA|messenger-RNA heteroduplexes, present in the binding sites of many RNA-binding proteins, and carried by endogenous small noncoding RNAs. Moreover, several of the motifs' intergenic copies overlap genome-wide association-study-determined polymorphisms associated with brain disorders and other conditions. Lastly, based on expression data from bulk brain samples from autism spectrum disorder patients and controls, specific combinations of these motifs are enriched only among genes that are downregulated in the patients and only in the cortical areas that are responsible for language, hearing, and vision. This study shows that genomic architecture, the sequences of ribosomal RNAs/spacers, and the sequences of nervous system genes have remained interlocked across 600 million years of evolution through organism-specific motifs. The findings suggest an extensive regulatory layer and can aid in developing new molecular diagnostics and treatments for disorders considered typically human.
Recommended Citation
Rigoutsos, Isidore; Nersisyan, Stepan; Londin, Eric; Nazeraj, Iliza; Dong, Bonnie; Vourekas, Anastasios; and Loher, Phillipe, "Organism-Specific Sequence Motifs Link Ribosomal RNAs to Brain Disorders" (2025). Computational Medicine Center Faculty Papers. Paper 64.
https://jdc.jefferson.edu/tjucompmedctrfp/64
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License
PubMed ID
41077723
Language
English
Included in
Computational Biology Commons, Computational Neuroscience Commons, Genetic Phenomena Commons, Nervous System Diseases Commons
Comments
This article is the author’s final published version in Molecular Biology and Evolution, Volume 42, Issue 10, 2025, Article number msaf237.
The published version is available at https://doi.org/10.1093/molbev/msaf237. Copyright © The Author(s) 2025.