Every messenger RNA molecule must be physically moved from the cell nucleus to the cytoplasm before it can direct protein production, and this research will map the hidden structural features that control how fast that journey happens. The problem is that while scientists know which proteins help shuttle mRNA out of the nucleus, they do not understand why different mRNAs leave at different speeds. The missing piece appears to be the three-dimensional shape of the RNA itself—its internal folds and loops—which is known to matter for other types of RNA but has been nearly impossible to study for mRNA inside living cells. Existing methods for disrupting the export process also tend to break the cell's transcription or translation machinery, making it hard to isolate export's specific role. The team will develop new techniques to capture single-molecule RNA structures in both the nucleus and cytoplasm, then train artificial intelligence models to identify the structural motifs that determine export efficiency. They will also investigate how RNA structure formed during transcription influences export, and whether export rates affect cell identity. This is fundamental science. If successful, it will provide a new framework for understanding a core step in gene expression—one that could eventually inform how cells regulate their own behaviour, or how defects in export contribute to disease.
View original technical description
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 export role 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.
Plain English summaries and category classifications on this site are generated by AI and may not perfectly reflect the original research.
Is something wrong? Let us know