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Characterisation of the molecular mechanisms determining the rna nuclear export pathways


Cells use distinct mechanisms to move different classes of RNA from their nuclear site of synthesis to the cytoplasm, including mRNA and U snRNA. Major spliceosomal U snRNAs and mRNAs share similarities in their synthesis : their precursors are transcribed in the nucleus by RNA polymerize II and acquire a m7G cap structure, bound by the nuclear cap-binding complex (CBC). Despite these similarities and the fact that in both cases there are no conserved internal RNA sequences required for nuclear export, U snRNAs and mRNAs are exported in metazoa by different factors. U snRNAs are exported in a complex containing CBC, PHAX (phosphorylated adaptor for RNA export), the export receptor CRM1/Xpo1 and the GTPase Ran. Interestingly, export of mRNAs does not require these factors but depends upon the REF and TAP/NXF1 proteins . Thus , there must be distinguishing features of U snRNAs and mRNAs that are recognized by these cellular factors. One obvious difference is that rnRNA precursors often contain introns whereas u snRNAs do not. It is particularly intriguing to investigate if the presence of an intron can commit a U snRNA to the rnRNA nuclear export pathway and determine if the mRNA specific factors imprinted onto the RNA during splicing can remodel the U1snRNA export. The aim of this project is to understand the molecular mechanisms that determine the two RNA nuclear export pathways and provide new insights as to how the export pathways are distinguished.


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