Investigation of the PTB-dependent RNA operon that regulates cytoskeletal organisation and cell migration. (360G-Wellcome-091595_Z_10_Z)

Messenger RNAs are subject to post-transcriptional control by a number distinct of mechanisms. Expression of the corresponding proteins can be regulated by changes in the rate of the mRNA degradation, and by transport of the mRNA to a specific cellular location. Cytoplasmic post-transcriptional control is tightly regulated by defined groups of mRNA binding proteins and it has been suggested that specific RNA-operons , comprised of RNA motifs and their cognate RNA binding proteins, ensure co-r egulated synthesis of proteins with common functions. To define the PTB-operon we have carried out polysome profiling following a reduction in PTB expression in conjunction with RNA co-immuno-precipitation using a PTB specific antibody to identify the mRNAs that bind to PTB and/or are dependent upon this protein for efficient translation. Approximately 25% of the mRNAs identified by these screens have a role in cytoskeletal organisation/cell migration. Our data suggest that PTB controls both the translation and the localisation of these mRNAs. The overall aims of this project are to identify the RNA elements and the proteins (in addition to PTB) that comprise the PTB operon and are involved in the post-transcriptional regulation of mRNAs that have a role in cytoskeletal organisation and cell migration.