VENTURE: Investigating the role of RNA structure in mRNA Export

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mRNA export is a key step in gene expression, tightly linked with both transcriptional and post-transcriptional processes. Previous studies have defined many export-associated proteins. Individual mRNAs can have distinct export rates even using the same proteins, but the rate-controlling mechanisms are unknown. RNA structure, as an important feature of RNA molecules, plays an essential exportrole for tRNA and rRNA. However, the role of RNA structure in mRNA export is unknown, mainly due to limitations in determining export-associated RNA structure motifs for mRNAs in living cells. Furthermore, mutating export-associated proteins that either abolish all mRNA export and impair the coupled transcription or translation processes, pose challenges for dissecting the function of mRNA export. We will develop several novel methods to generate a Big Data atlas of in vivo single-molecular RNA structure landscapes to compare nuclear and cytosolic RNAs. We will develop AI models to learn export-associated RNA structure motifs. We will also elucidate novel mechanistic insights into the role of RNA structure during transcription for facilitating mRNA export and uncover the underpinning functional importance of mRNA export, such as influencing cell identity. We will harness multidisciplinary methods to comprehensively investigate the role of RNA structure in mRNA export, from single mRNAs to the transcriptome level, from underpinning molecular mechanisms to phenotypic impacts, from individual investigation to Big Data mining. Both knowledge and technology advances derived from this programme will revolutionarily transform our current understanding and research approaches. The potential biological function of mRNA export in regulating cell identity in our work will shed light on our understanding of this remarkable evolutionary nucleus-cytoplasm compartmentalization. Both novel technologies and new frameworks will have the potential for translation to a broad range of organisms.