Binding interactions of the mRNA regulator CELF1
Edwards, John Michael (2013) Binding interactions of the mRNA regulator CELF1. PhD thesis, University of Nottingham.
CELF1 is an RNA binding protein with regulatory roles in translation, alternative splicing and mRNA degradation. This protein is of particular interest as its upregulation is believed to be involved in the pathogenesis of type 1 myotonic dystrophy. CELF1 functions by binding to a specific sequence in the 3’ untranslated region of its target mRNAs. This sequence has been termed the “EDEN” motif, but the exact requirements for binding of CELF1 were not well defined. In this study we therefore aimed to determine the sequence requirements for an RNA substrate to form a high affinity interaction with CELF1, and characterise the structure of the resulting complex. The CELF1 protein is composed of three structured RNA recognition motifs separated by flexible linkers. Our strategy was to investigate the RNA binding properties of each domain in isolation, and then the requirements for tandem binding of the domains in order to build up the complete “EDEN” motif capable of forming a high affinity complex with the wild type protein.
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