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

Nature Cell Biology volume 7, pages 1240–1247 (2005)Cite this article

An Erratum to this article was published on 02 December 2005

Abstract

We show that localized expression of the integrin α3 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 α3 to the adhesion complexes; MLP1 is localized in adhesion plaques that contain phospho-focal adhesion kinase; this localization is microtubule-dependent; integrin α3 transcripts colocalize with MLP1 in distinct cytoplasmic loci; integrin α3 transcripts are physically associated with MLP1 in cells and MLP1 binds to a specific ACACCC motif in the integrin α3 3′ untranslated region (UTR) in vitro; and a green fluorescent protein (GFP) open reading frame–integrin α3 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 α3 signal peptide.

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Figure 1: MLP1 regulates integrin α3 expression at the post-transcriptional level.
Figure 2: MLP1 is necessary for integrin α3 protein localization to adhesion plaques.
Figure 3: MLP1 regulates localization of integrin α3 RNA.
Figure 4: MLP1 interacts with integrin α3 3′ untranslated region (UTR) in vivo and in vitro.
Figure 5: Localized GFP expression mediated by the zipcode in integrin α3 3′ UTR.

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Acknowledgements

The work was supported by a Department of Defense Phase V Research Grant to Y.A., a Department of Defense Phase VII Geo Center grant to V.D., a grant from the National Cancer Institute (K22CA109577) to R.L., and grants from National Cancer Institute (RO1CA109860 and PO1CA78582) to T.H.

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  1. Department of Pathology and Laboratory Medicine, and Hollings Cancer Center, Medical University of South Carolina, 86 Jonathan Lucas St, Room 330, Charleston, 29425, SC, USA

    Yair Adereth, Vincent Dammai, Nurgun Kose, Runzhao Li & Tien Hsu

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  1. Yair Adereth
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Correspondence to Tien Hsu.

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Adereth, Y., Dammai, V., Kose, N. et al. RNA-dependent integrin α3 protein localization regulated by the Muscleblind-like protein MLP1. Nat Cell Biol 7, 1240–1247 (2005). https://doi.org/10.1038/ncb1335

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