Human La's Nuclear Retention Element Functions in La-RNA Target Discrimination
Marrella, Stefano Alessandro
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The La protein is an abundant RNA processing protein located in the nucleus of eukaryotic cells. Removal of the -helical nuclear retention element domain in human La causes the inappropriate export of these hLa-NRE mutants from the nucleus, resulting in the accumulation of non-functional aberrantly processed tRNAs within the cytoplasm. We hypothesized that the inappropriate nuclear export of hLa-NRE may be an indirect consequence of altered RNA target binding in cells. Electrophoretic mobility shift assays revealed hLa-NRE mutants exhibiting diminished binding affinity for precursor tRNAs in comparison to wild-type human La, however no differences in affinity were seen with poly A target binding. From this, we proposed a hypothetical model which suggests the cause for export of hLa-NRE mutants is a result of competitive binding with mRNA targets in the nucleus. This competition for binding results in the inappropriate export of these mutants with mRNA targets in a crm1-dependant manner.