Ringel, I.; (2009) Structural studies of RNA localisation signals. Doctoral thesis , UCL (University College London).

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Abstract

Asymmetric localisation of cytoplasmic mRNA in the cell appears in a variety of organisms and is important for establishment of spatially differential expression of genes. Localised transcripts typically contain codes (localisation signals), expressed within cis-acting elements that specify subcellular targeting. These signals are recognised by a complex of adaptor and motor proteins that move along the cytoskeleton. Cis-acting elements usually present in the 3'-UTRs of localising transcripts. Different signals do not appear to share either primary or secondary structures that are distinct from non-localising transcripts. Although secondary structure is important, the structural basis of the elements that contribute to the specificity of the localising transcripts is poorly understood. The presented thesis examines the basis of selective RNA transport, by studying the shortest signal known to drive localisation in Drosophila Melanogaster, a 44 nucleotides sequence on the 3' UTR of the fs(1)K10 transcript. This signal is necessary and sufficient for its localisation during embryo development and has a structure of stem loop with two unpaired bases ("bulges"). The components that are important for signal activity are analysed by studying the effect of specific mutations on localisation in the embryo and on the corresponding structure of the RNA. Using NMR structure solution, the importance of the two bulges is demonstrated in wild type and mutated signals and a new structural element of an unusual B-form-like double-stranded RNA helix is revealed. This unusual helix form subsequently been shown to be crucial for the localisation of the K10 transcript. These features might be important as representatives of a general structure that characterise a common group of localising transcripts.

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