Concentration and localization of co-expressed ELAV/Hu proteins control specificity of mRNA processing

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Colleges, School and Institutes

Abstract

Neuronally co-expressed ELAV/Hu proteins comprise a family of highly related RNA binding proteins, which bind to very similar cognate sequences. How this redundancy is linked to in vivo function and how gene specific regulation is achieved, has not been clear. Analysis of mutants in \(Drosophila\) ELAV/Hu family proteins ELAV, FNE and RBP9, and genetic interactions among them, indicates mostly independent roles in neuronal development and function, but convergence in the regulation of synaptic plasticity. Conversely, ELAV, FNE, RBP9 and human HuR bind ELAV target RNA in vitro with similar affinity. Likewise, all can regulate alternative splicing of ELAV target genes in non-neuronal wing-disc cells and substitute ELAV in eye development with artificially increased expression, but can also substantially restore ELAV's biological functions, when expressed under the control of the elav gene. Furthermore, ELAV related Sex-lethal can regulate ELAV targets and ELAV/Hu proteins can interfere with sexual differentiation. An ancient relationship to Sex-lethal is revealed by gonadal expression of RBP9 providing a maternal failsafe for dosage compensation. Our results indicate that highly related ELAV/Hu RNA binding proteins select targets for mRNA processing based on expression levels and sub-cellular localization, but only minimally by altered RNA binding specificity.

Details

Original languageEnglish
JournalMolecular and Cellular Biology
Publication statusPublished - 2015