RNA-dependent integrin α3 protein localization regulated by the Muscleblind-like protein MLP1

We show that localized expression of the integrin alpha(3) protein is regulated at the level of RNA localization by the human homologue of Drosophila Muscleblind, MLP1/MBLL/MBNL2, a unique Cys(3)His zinc-finger protein. This is supported by the following observations: MLP1 knockdown abolishes localization of integrin alpha(3) to the adhesion complexes; MLP1 is localized in adhesion plaques that contain phospho-focal adhesion kinase; this localization is microtubule-dependent; integrin alpha(3) transcripts colocalize with MLP1 in distinct cytoplasmic loci; integrin alpha(3) transcripts are physically associated with MLP1 in cells and MLP1 binds to a specific ACACCC motif in the integrin alpha(3) 3' untranslated region (UTR) in vitro; and a green fluorescent protein (GFP) open reading frame-integrin alpha(3) 3' UTR chimeric gene directs GFP protein localization to distinct cytoplasmic loci near the cell periphery, which is dependent on MLP1 and is mediated by the ACACCC motif but is independent of the integrin alpha(3) signal peptide.