28S-rsRNA facilitates PASMC proliferation through PKM2 β-hydroxybutyrylation

28S rsRNA-CTC_L20 is upregulated in hypoxic PASMCs and pulmonary hypertension models and promotes PASMC proliferation, with knockdown mitigating SuHx-induced pulmonary hypertension and vascular remodeling.

• Why it matters: rsRNAs from rRNA are linked to disease biology, but their roles in pulmonary hypertension and hypoxia-driven vascular remodeling are not well defined.
• What they did: The study identified 28S rsRNA-CTC_L20 and tested its effects in hypoxic PASMCs and in SuHx-induced PH, then mapped a pathway where it maintains ketogenic enzyme mRNA stability via a CTGNNGG motif to modulate BHB production.
• The result: Increased BHB enhances PKM2 β-hydroxybutyrylation at K166, raising PKM2 activity and glycolysis to support proliferation, defining an rsRNA–BHB–PKM2 β-hydroxybutyrylation axis and suggesting 28S rsRNA-CTC_L20 as a therapeutic target.

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