Completed Genetics & Molecular Biology Cells, Biochemistry & Physiology

RNA metabolism in developing neurons

Funder Wellcome Charity-funded
Recipient organisation University College London
Funding £2.1M
Period Nov 2019 — Oct 2024

In plain English

AI plain-English summary

A single molecule of RNA can carry two conflicting instructions, and scientists want to know how a developing nerve cell decides which one to follow. Neurons must build different proteins in different parts of the cell—at the tip of a growing axon, for instance, versus the cell body. Most research has focused on how genes are switched on and off, but errors in the later steps of RNA processing and delivery are known to cause severe neurological disorders. This project investigates how the 3’ untranslated region (3’UTR) of an RNA molecule—a stretch of genetic material that does not code for protein—governs whether that RNA is spliced, exported from the nucleus, or sent to a specific location. The team has already mapped which 3’UTRs appear in different compartments of sympathetic neurons and will now test whether these regions can generate a new class of regulatory RNAs that guide development. This is fundamental science. It will not produce a drug or a diagnostic tomorrow. But understanding how a single mRNA can have two fates—and how the 3’UTR controls that choice—could eventually explain why certain mutations in non-coding RNA cause developmental brain disorders, and point toward entirely new targets for intervention.

View original technical description
Understanding how neurons translate extracellular cues into specific patterns of gene expression is amongst the major goals of modern neurobiology. Efforts to unravel the molecular basis of localised gene expression have mostly focused on transcriptional control and mRNA transport. However, post-transcriptional mRNA processing is increasingly recognised as an essential step in the propagation of genetic information. Importantly, incorrect processing and delivery of mRNA causes developmental defects and severe human neurological disorders. The overarching scope of this project is to investigate novel mechanisms of mRNA metabolism that are likely to be conserved in all mammalian cells and to provide new insights regarding how gene expression is regulated in neurons. The 3’ untranslated regions (3’UTRs) of RNA transcripts play a key role in mediating many steps of RNA metabolism, including splicing, nuclear export and localization. We performed 3’end-Seq screens of transcripts localised in sub-cellular compartments of sympathetic neurons and are uniquely positioned to tackle the question of how 3’UTRs regulate RNA metabolism in neurons. We will address the following questions: - What determines the fate of a bifunctional mRNA? - Does the 3’UTR influence the proteome in sympathetic neurons? - Do 3’UTRs generate a new class of RNAs that regulate neuronal development?

View the original record at the funder ↗

Researchers

Antonella Riccio (EPMC Awardee)

Related Research

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Original classification

Investigator Award in Science

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