BIOLOGICAL ROLE OF MITOCHONDRIAL RIBOSOMAL PROTEIN
- 1Universidade de São Paulo, São Paulo, SP, Brazil
- 2University Medical Center Groningen, Netherlands
Abstract
Background: Acute myeloid leukemia (AML) exhibits enhanced oxidative phosphorylation (OXPHOS) capacity dependent on mitochondrial DNA (mtDNA) copy number. We previously developed a prognostic risk score based on mtDNA modulators, including MRPL21, which is essential for myeloid cell viability; however, its specific biological roles in AML remain underexplored. Aim: To investigate the biological roles of MRPL21 in AML. Methods: Three independent public cohorts (TCGA, BeatAML, and CPTAC multi-omic cohort) were used for transcriptomic and proteomic analyses, including WGCNA, Gene Ontology, GSEA, and CIBERSORTx. scRNA-seq data from healthy and AML bone marrow (BM) were analyzed to identify DEGs and MRPL21-associated transcriptomic signatures. Significance was set at p-value and FDR<0.05, and |NES|>1.5. Results and discussion: Across all public cohorts, MRPL21 overexpression upregulated rRNA and tRNA metabolism (from processing to quality control), mitochondrial and cytoplasmic translation, and OXPHOS in both transcriptomic and proteomic profiles. Furthermore, cellular deconvolution analysis showed an enrichment of quiescent leukemic stem cells in MRPL21-high samples. scGSEA confirmed these biosynthetic and energetic signatures in both leukemic and healthy BM. Within AML, MRPL21-high cells exhibited enrichment in global and mitochondrial translation, constitutive RNA processing and replication, and positive regulation of the cytoskeleton, particularly in erythroid clusters. The scRNA-seq revealed diffuse MRPL21 expression across all myeloid clusters; however, target gene expression was decreased in AML compared to healthy BM, peaking in early and late erythroid cells. The early erythroid cluster retained the highest proportion of MRPL21-high cells in AML, with these cells showing upregulation of DNA maintenance and mitochondrial homeostasis genes, aligning with the top correlated genes in bulk RNA-seq findings. Other differentially expressed genes associated with MRPL21 were involved in cell cycle progression as well as nucleic acid and protein metabolism in both healthy and leukemic bone marrow. Conclusion: These findings suggest that MRPL21 overexpression is closely linked to increased constitutive RNA metabolism, translation, and OXPHOS signatures, highlighting its biological relevance in AML.
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BibTeX
@article{santos2026biological,
title = {{BIOLOGICAL ROLE OF MITOCHONDRIAL RIBOSOMAL PROTEIN}},
author = {Isabelle Caroline SANTOS and Juan Luiz COELHO-SILVA and Diego Antonio PEREIRA-MARTINS and João Agostinho MACHADO-NETO},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.107562},
url = {https://doi.org/10.1016/j.htct.2026.107562},
note = {CC BY},
}
RIS
TY - JOUR
TI - BIOLOGICAL ROLE OF MITOCHONDRIAL RIBOSOMAL PROTEIN
AU - Isabelle Caroline SANTOS
AU - Juan Luiz COELHO-SILVA
AU - Diego Antonio PEREIRA-MARTINS
AU - João Agostinho MACHADO-NETO
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.107562
UR - https://doi.org/10.1016/j.htct.2026.107562
AB - Background: Acute myeloid leukemia (AML) exhibits enhanced oxidative phosphorylation (OXPHOS) capacity dependent on mitochondrial DNA (mtDNA) copy number. We previously developed a prognostic risk score based on mtDNA modulators, including MRPL21, which is essential for myeloid cell viability; however, its specific biological roles in AML remain underexplored. Aim: To investigate the biological roles of MRPL21 in AML. Methods: Three independent public cohorts (TCGA, BeatAML, and CPTAC multi-omic cohort) were used for transcriptomic and proteomic analyses, including WGCNA, Gene Ontology, GSEA, and CIBERSORTx. scRNA-seq data from healthy and AML bone marrow (BM) were analyzed to identify DEGs and MRPL21-associated transcriptomic signatures. Significance was set at p-value and FDR<0.05, and |NES|>1.5. Results and discussion: Across all public cohorts, MRPL21 overexpression upregulated rRNA and tRNA metabolism (from processing to quality control), mitochondrial and cytoplasmic translation, and OXPHOS in both transcriptomic and proteomic profiles. Furthermore, cellular deconvolution analysis showed an enrichment of quiescent leukemic stem cells in MRPL21-high samples. scGSEA confirmed these biosynthetic and energetic signatures in both leukemic and healthy BM. Within AML, MRPL21-high cells exhibited enrichment in global and mitochondrial translation, constitutive RNA processing and replication, and positive regulation of the cytoskeleton, particularly in erythroid clusters. The scRNA-seq revealed diffuse MRPL21 expression across all myeloid clusters; however, target gene expression was decreased in AML compared to healthy BM, peaking in early and late erythroid cells. The early erythroid cluster retained the highest proportion of MRPL21-high cells in AML, with these cells showing upregulation of DNA maintenance and mitochondrial homeostasis genes, aligning with the top correlated genes in bulk RNA-seq findings. Other differentially expressed genes associated with MRPL21 were involved in cell cycle progression as well as nucleic acid and protein metabolism in both healthy and leukemic bone marrow. Conclusion: These findings suggest that MRPL21 overexpression is closely linked to increased constitutive RNA metabolism, translation, and OXPHOS signatures, highlighting its biological relevance in AML.
SN - 2531-1379
SN - 2531-1387
ER -