This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kay, R. A. Articles by Schor, S. L. Search for Related Content PubMed PubMed Citation Articles by Kay, R. A. Articles by Schor, S. L.

The Expression of Migration Stimulating Factor, a Potent Oncofetal Cytokine, Is Uniquely Controlled by 3'-Untranslated Region–Dependent Nuclear Sequestration of Its Precursor Messenger RNA

Unit of Cell and Molecular Biology, Dental School, University of Dundee, Dundee, United Kingdom

Requests for reprints: Seth L. Schor, Unit of Cell and Molecular Biology, Dental School, University of Dundee, Dundee DD1 4HR, United Kingdom. Phone: 44-1382-635991; Fax: 44-1382-635998; E-mail: S.L.Schor{at}dundee.ac.uk.

Migration stimulating factor (MSF) is a truncated oncofetal fibronectin isoform expressed by fetal and tumor-associated cells. MSF mRNA is distinguished from other fibronectin isoforms by its size (2.1 kb) and the inclusion of a specific intronic sequence at its 3' end. Initial Northern blot analysis with a MSF-specific probe indicated the presence of this 2.1-kb transcript and an additional unexpected 5.9-kb RNA present in both MSF-secreting (fetal) and nonsecreting (adult) fibroblasts. Our investigations into the nature of these transcripts and their relationship to MSF protein secretion revealed that the 5.9-kb mRNA is a second MSF-encoding transcript. Both these mRNAs have identical coding sequence and differ only in the length of their intron-derived 3'-untranslated region (UTR). The 5.9-kb MSF mRNA is retained in the nucleus whereas the 2.1-kb mRNA is not. MSF-secreting fetal fibroblasts have significantly lower nuclear levels of the 5.9-kb mRNA and correspondingly higher cytoplasmic levels of the 2.1-kb transcript than their nonsecreting adult counterparts. Adult fibroblasts induced to secrete MSF by treatment with transforming growth factor-ß1 displayed similar changes in their respective levels of MSF mRNA, but not those of a control gene. When cloned downstream of a reporter gene, only the longer 3'-UTR retained coding sequence within the nucleus. We conclude that expression of MSF protein is regulated by 3'-UTR truncation of the 5.9-kb nuclear-sequestered "precursor" MSF mRNA and nuclear export of mature 2.1-kb message. Inducible 3'-UTR processing represents a novel regulatory mechanism involved in cancer pathogenesis that may open new avenues for therapeutic gene delivery.

This article has been cited by other articles:

				L. J. Terry, E. B. Shows, and S. R. Wente Crossing the Nuclear Envelope: Hierarchical Regulation of Nucleocytoplasmic Transport Science, November 30, 2007; 318(5855): 1412 - 1416. [Abstract] [Full Text] [PDF]

				K. V. Prasanth and D. L. Spector Eukaryotic regulatory RNAs: an answer to the 'genome complexity' conundrum Genes & Dev., January 1, 2007; 21(1): 11 - 42. [Abstract] [Full Text] [PDF]