RNA-dependent integrin alpha3 protein localization regulated by the Muscleblind-like protein MLP1.
We show that localized expression of the integrin alpha3 protein is regulated at the level of RNA localization by the human homologue of Drosophila Muscleblind, MLP1/MBLL/MBNL2, a unique Cys3His zinc-finger protein. This is supported by the following observations: MLP1 knockdown abolishes localization of integrin alpha3 to the adhesion complexes; MLP1 is localized in adhesion plaques that contain phospho-focal adhesion kinase; this localization is microtubule-dependent; integrin alpha3 transcripts colocalize with MLP1 in distinct cytoplasmic loci; integrin alpha3 transcripts are physically associated with MLP1 in cells and MLP1 binds to a specific ACACCC motif in the integrin alpha3 3' untranslated region (UTR) in vitro; and a green fluorescent protein (GFP) open reading frame-integrin alpha3 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 alpha3 signal peptide.
Adereth
Yair
Y
Department of Pathology and Laboratory Medicine, and Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, Room 330, Charleston, SC 29425, USA.
Dammai
Vincent
V
Kose
Nurgun
N
Li
Runzhao
R
Hsu
Tien
T
D000595:Amino Acid Sequence; D001665:Binding Sites; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D039422:Integrin alpha3 / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008870:Microtubules; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000502:physiology*; D014162:Transfection; D016335:Zinc Fingers
D039422:Integrin alpha3; C493663:MBNL1 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D049452:Green Fluorescent Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases