RiboMeth-Sequencing Reveals Selective Ribosomal RNA 2′-O-Methylation Changes in the Dorsolateral Prefrontal Cortex of Subjects With Major Depressive Disorder
- 1Department of Psychiatry and Behavioral Neurobiology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama
- 2Address correspondence to Yogesh Dwivedi, Ph.D.
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: RiboMeth-seq was performed in the dorsolateral prefrontal cortex of individuals with MDD ( n = 17) and matched nonpsychiatric control subjects ( n = 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.
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BibTeX
@article{verma2026ribomethsequencing,
title = {{RiboMeth-Sequencing Reveals Selective Ribosomal RNA 2′-O-Methylation Changes in the Dorsolateral Prefrontal Cortex of Subjects With Major Depressive Disorder}},
author = {Anuj K. Verma and Bhaskar Roy and Kevin Prall and Yogesh Dwivedi},
journal = {Biological Psychiatry Global Open Science},
year = {2026},
month = sep,
doi = {10.1016/j.bpsgos.2026.100832},
url = {https://doi.org/10.1016/j.bpsgos.2026.100832},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - RiboMeth-Sequencing Reveals Selective Ribosomal RNA 2′-O-Methylation Changes in the Dorsolateral Prefrontal Cortex of Subjects With Major Depressive Disorder
AU - Anuj K. Verma
AU - Bhaskar Roy
AU - Kevin Prall
AU - Yogesh Dwivedi
PY - 2026
DA - 2026/09/22
JO - Biological Psychiatry Global Open Science
DO - 10.1016/j.bpsgos.2026.100832
UR - https://doi.org/10.1016/j.bpsgos.2026.100832
AB - 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: RiboMeth-seq was performed in the dorsolateral prefrontal cortex of individuals with MDD ( n = 17) and matched nonpsychiatric control subjects ( n = 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.
SN - 2667-1743
ER -