8d ago
Temozolomide Induces Aberrant RNA Alkylation and Widespread Translational Repression
Rhodes · J. · Johnston · A. G. · Brazell · K. M. · Liu · X. · +4 more
Abstract
Temozolomide (TMZ) is a frontline alkylating chemotherapy, yet its direct impact on RNA modification and global translation dynamics remains poorly understood. Here, we demonstrate that TMZ induces pervasive RNA alkylation causing severe translational impairment. TMZ directly deposits aberrant methyl groups onto single-stranded mRNA in vitro, creating physical lesions that lower translational efficiency. In glioblastoma cells, acute TMZ exposure triggers a rapid, widespread accumulation of m7G o
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