Emerin interacts in vitro with the splicing‐associated factor, YT521‐B

Emerin is a nuclear membrane protein that interacts with lamin A/C at the nuclear envelope. Mutations in either emerin or lamin A/C cause Emery–Dreifuss muscular dystrophy (EDMD). The functions of emerin are poorly understood, but EDMD affects mainly skeletal and cardiac muscle. We used a high‐stringency yeast two‐hybrid method to screen a human heart cDNA library, with full‐length emerin as bait. Four out of five candidate interactors identified were nuclear proteins: lamin A, splicing factor YT521‐B, proteasome subunit PA28γ and transcription factor vav‐1. Specific binding between emerin and the functional C‐terminal domain of YT521‐B was confirmed by pull‐down assays and biomolecular interaction analysis (BIAcore). Inhibition by emerin of YT521‐B‐dependent splice site selection in vivo suggests that the interaction is physiologically significant. A ‘bipartite’ binding site for YT521‐B in emerin was identified using alanine substitution or disease‐associated mutations in emerin. The transcription factor GCL (germ cell‐less) has previously been shown to bind to the same site. The results are consistent with an emerging view that lamins and lamina‐associated proteins, like emerin, have a regulatory role, as well as a structural role in the nucleus. YT521‐B joins a growing list of candidates for a role in a gene expression model of the pathogenesis of EDMD.