Determining spatial arrangement, stoichiometry, and substrate specificity of messenger RNA-binding proteins along the gene expression pathway.

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The long-term objective of our research program is to study the maturation pathways of essential RNA-protein complexes in different organisms. The expression of our genes is tightly regulated both during the reading and copying of our DNA into messenger RNA (mRNA), the encoding template, and during translation, when the information in this template is converted into proteins. However, transcription and translation are not the only steps where regulation and alteration of our genetic material can occur. mRNA itself is bound by many proteins that further process, fold and inspect the molecule to ensure its correctness and hence the correct transmission of genetic code into proteins for diverse processes in the cell. While it has been assumed that all mRNA molecules are uniformly processed, or matured, by the same set of proteins, recent data from our lab suggests that there may be variation in these maturation steps that are defined by the variance in proteins associating with different mRNAs during these steps. This project proposes to further explore these suggested variances in mRNA maturation, by investigating the mRNAs involved, the underlying mechanisms that lead to variances, and their consequences, as any misstep in this process could lead to the introduction of errors resulting in disease. Overall, a more detailed basic knowledge of any additional regulatory steps during the expression of our genetic material will provide us with better fundamental understanding of gene regulation as well as why certain diseases may develop and potential new entry points for treatment in the future.