SMD2 reads pseudouridines to regulate mRNA splicing and promote tumorigenesis.

SMD2, a core spliceosomal protein, directly reads pseudouridines in mRNA to regulate splicing and promote tumor growth, with SNRPD2 overexpressed in multiple cancers.

• Why it matters: Understanding how pseudouridines influence splicing is crucial because their regulatory mechanisms are largely unknown, hindering potential therapeutic advances in cancer treatment.
• What they did: The study identified SMD2 as a pseudouridine reader through in vitro and ex vivo assays, demonstrating its preferential binding to pseudouridine-modified RNA and collaboration with PUS enzymes to control alternative splicing.
• The result: SNRPD2 overexpression is essential for tumor cell proliferation, linking pseudouridine recognition to mRNA maturation and positioning SMD2 as a promising target for cancer therapy.