Long non-coding RNA RMRP undergoes magnesium-dependent structural changes that enable specific binding to DEAD-box helicases DDX5 and DDX3X, which facilitate its transport to mitochondria where it influences cellular energy production. The helicases show distinct binding patterns and RNA-unwinding capabilities when partnered with RMRP. This discovery illuminates a previously unknown pathway connecting RNA regulatory networks to mitochondrial metabolism, potentially explaining why RMRP mutations cause cartilage-hair hypoplasia and related disorders. The finding positions long non-coding RNAs as direct modulators of cellular powerhouses rather than mere gene expression regulators. Given mitochondrial dysfunction's central role in aging and age-related diseases, understanding how specific lncRNAs like RMRP coordinate energy metabolism could reveal new therapeutic targets. The magnesium-dependency suggests environmental factors affecting cellular mineral status might influence this regulatory axis. While this represents fundamental mechanistic insight, translating these molecular interactions into clinical interventions remains distant, requiring validation across disease contexts and development of RNA-targeting therapeutics that can effectively reach mitochondrial compartments.