RiboMeth-Sequencing Reveals Selective Ribosomal RNA 2′-O-Methylation Changes in the Dorsolateral Prefrontal Cortex of Subjects With Major Depressive Disorder
Year: 2026
Type: article
Study design: Observational Study
Abstract: Background: Major depressive disorder (MDD) is associated with widespread molecular abnormalities in the brain; however, the contribution of ribosome-centered regulatory mechanisms remains poorly understood. Ribosomal RNA (rRNA) 2'-O-methylation (Nm) is the most abundant and evolutionarily conserved RNA modification and has emerged as a determinant of ribosome heterogeneity and translational control. However, the rRNA Nm landscape has not been examined in psychiatric illness. Here, we used RiboMeth-seq to map site-specific rRNA Nm in the MDD brain. Methods: = 20) using an Illumina NextSeq2000 in 50-bp single-end mode. Specific RiboMeth-seq scores were calculated in ±2 nucleotide intervals for all RNA positions and extracted for the positions of known Nm residues in target RNA. Results: The overall distribution of ribose methylation scores was highly similar between groups, indicating the preservation of the global rRNA Nm landscape in MDD. At the same time, we identified 8 significantly altered Nm sites, including 4 in 28S rRNA (Am2802, Cm2848, Cm3866, and Gm4593) and 4 in 18S rRNA (Um172, Am576, Am1031, and Gm1490). These selective changes occurred in the absence of widespread remodeling, supporting a model in which MDD is associated with targeted modification of functionally relevant ribosomal positions rather than a generalized disruption of ribosome integrity. Conclusions: Our findings identify rRNA Nm as a previously unrecognized layer of molecular alteration in MDD and suggest that site-specific variation in ribosome composition may contribute to aberrant translational regulation in the depressed brain.
Institutions: University of Alabama at Birmingham, UAB Medicine
Language: English
Topic: RNA modifications and cancer
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,700
Awards: Epitranscriptomic Mapping of Novel N6-Adenosine-based RNA Methylation in MDD Brain, G2458790829, G3618992063, G6149264481, G6697359561, G6930204474, Plasma Exosomal MicroRNAs as Promising Novel Biomarkers for Suicidality and Treatment Outcome, Novel cell type-specific epigenetic role of nuclear lncRNAs in 3D heterochromatization and transcriptional repatterning in the MDD brain, MicroRNA Correlates of Childhood Maltreatment and Suicidality, Novel regulatory role of nuclear miRNAs in repatterning the transcriptional and post-transcriptional dynamics in MDD brain, Neural-Derived Plasma Exosomal MicroRNAs As Promising Novel Biomarkers for Suicidality and Treatment Outcome in Adolescents
OpenAlex ID: W7213973442