Investigating the function of novel cis-regulatory elements in 3'UTRs of mRNAs and their molecular mechanisms in post-transcriptional gene regulation.

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A variety of post-transcriptional regulatory mechanisms significantly contribute to gene expression and ultimately alter the amount of synthesized protein. Post-transcriptional regulation is mediated by cis-regulatory elements, typically located within the untranslated regions (UTRs) of mRNAs, and trans-acting factors that bind to these elements. A genome-wide comparative study indicates the existence of hundreds of novel potential cis-regulatory elements within 3¿UTRs. Although several post-transcriptional regulatory mechanisms have been elucidated, the prevalence of these elements supposes many additional pathways to be discovered. This project aims to identify and analyze the underlying molecular mechanisms of novel post-transcriptional gene regulatory elements. First, their mode of action will be examined by genetic and biochemical assays, to determine if they regulate mRNA maturation, export into the cytoplasm, sub-cellular localization, stability and/or translation. Second, the trans-acting factors, presumably proteins, required for novel cis-element regulation, will be identified by using both a candidate gene approach and whole-genome RNAi-based screening. Since the cis-regulatory elements, we propose to study, are present in many different mRNAs, the discoveries of their mechanisms and trans-acting factors are expected to have broad significance to the regulation of gene expression.