The c-fos and c-myc 3’ Untranslated Regions are Multi-Functional Regulatory Regions Influencing mRNA Localisation and Stability

John Hesketh
Department of Biological & Nutritional Sciences
University of Newcastle
Newcastle-upon-Tyne
UK NE1 7RU
telephone: 44-191-222-8744
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presenter: John HESKETH

Dalgleish, G.D.1, Veyrune, J-L.2, Blanchard, J-M.2 and Hesketh, J.E.1,3
1Rowett Research Institute, Bucksburn, Aberdeen, AB21 9SB, UK
2IGMM, CNRS, 1818 Route de Mende, Montpellier, France
3Department of Biological and Nutritional Sciences, University of Newcastle, Kings Rd, Newcastle-upon-Tyne, NE1
7RU, UK

3’untranslated regions (3’UTR) are emerging as important in post-transcriptional control of gene expression, regulating mRNA stability, translation and localisation. The mRNAs encoding c-myc and c-fos are unstable and this instability is partly determined by sequences within the 3’UTR. C-myc mRNA is localised around the nucleus and both c-myc and c-fos mRNAs are found associated with the cytoskeleton. Studies with cells transfected with chimaeric reporter constructs in which 3’UTR sequences are linked to a ß-globin reporter show that both c-myc and c-fos 3’UTRs contain sequences capable of targeting globin to the cytoskeleton and the perinuclear cytoplasm. In both cases the part of the 3’UTR containing the localisation signal has been partly defined (to within 86nt for c- myc, to within 145 for c-fos) and the regions responsible are distinct from those that affect mRNA stability. Deletion analysis of the both 3’UTRs shows that removal of specific regions which affect mRNA localisation do not affect stability and vice versa. Thus, it appears that these two 3’UTRs contain multiple regulatory elements, one leading to mRNA instability and one to mRNA localisation. The nature of the RNA sequence/structure that forms the localisation signal is unknown. Furthermore, if translation is prevented localisation of the mRNA does not occur suggesting that some form of translation initiation complex is required for localisation of the mRNAs. Thus, the 3’UTRs of c-myc and c-fos play a key role in the post-transcriptional control of the expression of these genes and in determining the site of the synthesis of the encoded proteins.



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