Muscleblind-like proteins dimerize by forming disulfide bonds to influence regulation of alternative splicing

MBNL dimerization may play a role in these functions, but the mechanism is not well understood. Here we identify a cysteine residue in the unstructured carboxy-terminal domain of MBNL1 that enables dimerization by forming intermolecular disulfide bonds.

We also demonstrate that MBNL2 likewise dimerizes by forming disulfide bonds between multiple cysteines in its carboxy-terminal tail. Nucleocytoplasmic fractionation revealed a greater proportion of MBNL1 dimer in the nucleus, suggesting a nuclear function for the MBNL1 dimer. We investigated a connection between MBNL1 dimerization and MBNL1-mediated regulation of alternative splicing.