Mol. Cell. Biol., 01 1995, 235-245, Vol 15, No. 1
Copyright © 1995, American Society for Microbiology

Long-range RNA interaction of two sequence elements required for endonucleolytic cleavage of human insulin-like growth factor II mRNAs

W Scheper, D Meinsma, PE Holthuizen and JS Sussenbach
Laboratory for Physiological Chemistry, Utrecht University, The Netherlands.

Human insulin-like growth factor II (IGF-II) mRNAs are subject to site- specific endonucleolytic cleavage in the 3' untranslated region, leading to an unstable 5' cleavage product containing the IGF-II coding region and a very stable 3' cleavage product of 1.8 kb. This endonucleolytic cleavage is most probably the first and rate-limiting step in degradation of IGF-II mRNAs. Two sequence elements within the 3' untranslated region are required for cleavage: element I, located approximately 2 kb upstream of the cleavage site, and element II, encompassing the cleavage site itself. We have identified a stable double-stranded RNA stem structure (delta G = -100 kcal/mol [418.4 kJ/mol]) that can be formed between element I and a region downstream of the cleavage site in element II. This structure is conserved among human, rat, and mouse mRNAs. Detailed analysis of the requirements for cleavage shows that the relative position of the elements is not essential for cleavage. Furthermore, the distance between the coding region and the cleavage site does not affect the cleavage reaction. Mutational analysis of the long-range RNA-RNA interaction shows that not only the double-stranded character but also the sequence of the stable RNA stem is important for cleavage.

This article has been cited by other articles:

• Zekri, L., Chebli, K., Tourriere, H., Nielsen, F. C., Hansen, T. V. O., Rami, A., Tazi, J. (2005). Control of Fetal Growth and Neonatal Survival by the RasGAP-Associated Endoribonuclease G3BP. Mol. Cell. Biol. 25: 8703-8716 [Abstract] [Full Text]  
• Hibbert, C. S., Rein, A. (2005). Preliminary Physical Mapping of RNA-RNA Linkages in the Genomic RNA of Moloney Murine Leukemia Virus. J. Virol. 79: 8142-8148 [Abstract] [Full Text]  
• Ing, N. H. (2005). Steroid Hormones Regulate Gene Expression Posttranscriptionally by Altering the Stabilities of Messenger RNAs. Biol. Reprod. 72: 1290-1296 [Abstract] [Full Text]  
• Mawji, I. A., Robb, G. B., Tai, S. C., Marsden, P. A. (2004). Role of the 3'-Untranslated Region of Human Endothelin-1 in Vascular Endothelial Cells: CONTRIBUTION TO TRANSCRIPT LABILITY AND THE CELLULAR HEAT SHOCK RESPONSE. J. Biol. Chem. 279: 8655-8667 [Abstract] [Full Text]  
• Patel, N. A., Eichler, D. C., Chappell, D. S., Illingworth, P. A., Chalfant, C. E., Yamamoto, M., Dean, N. M., Wyatt, J. R., Mebert, K., Watson, J. E., Cooper, D. R. (2003). The Protein Kinase C beta II Exon Confers mRNA Instability in the Presence of High Glucose Concentrations. J. Biol. Chem. 278: 1149-1157 [Abstract] [Full Text]  
• Putland, R. A., Sassinis, T. A., Harvey, J. S., Diamond, P., Coles, L. S., Brown, C. Y., Goodall, G. J. (2002). RNA Destabilization by the Granulocyte Colony-Stimulating Factor Stem-Loop Destabilizing Element Involves a Single Stem-Loop That Promotes Deadenylation. Mol. Cell. Biol. 22: 1664-1673 [Abstract] [Full Text]  
• Paillart, J.-C., Skripkin, E., Ehresmann, B., Ehresmann, C., Marquet, R. (2002). In Vitro Evidence for a Long Range Pseudoknot in the 5'-Untranslated and Matrix Coding Regions of HIV-1 Genomic RNA. J. Biol. Chem. 277: 5995-6004 [Abstract] [Full Text]  
• Paulsen, M., Takada, S., Youngson, N. A., Benchaib, M., Charlier, C., Segers, K., Georges, M., Ferguson-Smith, A. C. (2001). Comparative Sequence Analysis of the Imprinted Dlk1-Gtl2 Locus in Three Mammalian Species Reveals Highly Conserved Genomic Elements and Refines Comparison with the Igf2-H19 Region. Genome Res. 11: 2085-2094 [Abstract] [Full Text]  
• Yu, J., Russell, J. E. (2001). Structural and Functional Analysis of an mRNP Complex That Mediates the High Stability of Human {beta}-Globin mRNA. Mol. Cell. Biol. 21: 5879-5888 [Abstract] [Full Text]  
• van Dijk, E. L., Sussenbach, J. S., Holthuizen, P. E. (2001). Kinetics and regulation of site-specific endonucleolytic cleavage of human IGF-II mRNAs. Nucleic Acids Res 29: 3477-3486 [Abstract] [Full Text]  
• Gaunt, T. R., Cooper, J. A., Miller, G. J., Day, I. N.M., O'Dell, S. D. (2001). Positive associations between single nucleotide polymorphisms in the IGF2 gene region and body mass index in adult males. Hum Mol Genet 10: 1491-1501 [Abstract] [Full Text]  
• Kenealy, M.-R., Flouriot, G., Sonntag-Buck, V., Dandekar, T., Brand, H., Gannon, F. (2000). The 3'-Untranslated Region of the Human Estrogen Receptor {alpha} Gene Mediates Rapid Messenger Ribonucleic Acid Turnover. Endocrinology 141: 2805-2813 [Abstract] [Full Text]  
• Sokolowski, M., Tan, W., Jellne, M., Schwartz, S. (1998). mRNA Instability Elements in the Human Papillomavirus Type 16 L2 Coding Region. J. Virol. 72: 1504-1515 [Abstract] [Full Text]  
• Bashkirov, V. I., Scherthan, H., Solinger, J. A., Buerstedde, J.-M., Heyer, W.-D. (1997). A Mouse Cytoplasmic Exoribonuclease (mXRN1p) with Preference for G4 Tetraplex Substrates. J. Cell Biol. 136: 761-773 [Abstract] [Full Text]