Hypoxia re-programs 2′-O-Me modifications on ribosomal RNA
Brandon J. Metge,
Sarah C. Kammerud,
Hawley C. Pruitt,
Lalita A. Shevde,
Rajeev S. Samant
Affiliations
Brandon J. Metge
Department of Pathology, University of Alabama at Birmingham, WTI 320E 1824 6th Avenue South, Birmingham, AL 35233, USA
Sarah C. Kammerud
Department of Pathology, University of Alabama at Birmingham, WTI 320E 1824 6th Avenue South, Birmingham, AL 35233, USA
Hawley C. Pruitt
Department of Pathology, University of Alabama at Birmingham, WTI 320E 1824 6th Avenue South, Birmingham, AL 35233, USA
Lalita A. Shevde
Department of Pathology, University of Alabama at Birmingham, WTI 320E 1824 6th Avenue South, Birmingham, AL 35233, USA; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA
Rajeev S. Samant
Department of Pathology, University of Alabama at Birmingham, WTI 320E 1824 6th Avenue South, Birmingham, AL 35233, USA; Birmingham VA Medical Center, Birmingham, AL, USA; Corresponding author
Summary: Hypoxia is one of the critical stressors encountered by various cells of the human body under diverse pathophysiologic conditions including cancer and has profound impacts on several metabolic and physiologic processes. Hypoxia prompts internal ribosome entry site (IRES)-mediated translation of key genes, such as VEGF, that are vital for tumor progression. Here, we describe that hypoxia remarkably upregulates RNA Polymerase I activity. We discovered that in hypoxia, rRNA shows a different methylation pattern compared to normoxia. Heterogeneity in ribosomes due to the diversity of ribosomal RNA and protein composition has been postulated to generate “specialized ribosomes” that differentially regulate translation. We find that in hypoxia, a sub-set of differentially methylated ribosomes recognizes the VEGF-C IRES, suggesting that ribosomal heterogeneity allows for altered ribosomal functions in hypoxia.
