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LMCB - Laboratory for Molecular Cell Biology

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Antonella Riccio's picture
LMCB Group Leader, UCL Professor of Neuroscience
 
+44 (0)20 7679 7814
LMCB Room 1.01A
 
Mechanisms of gene expression in neurons

Research synopsis

The proper wiring of the mammalian nervous system is a task of unique complexity, which requires specific point-to-point connections between billions of neurons.  
 
At the heart of this fundamental biological process lies the ability of environmental cues to regulate the expression of specific genes that encode proteins that promote neuronal survival, axon growth, differentiation, synapse formation, and, later, synaptic plasticity.  Two major regulatory events influence gene expression: binding and activation of nuclear proteins to cis-acting regulatory elements in gene promoters and epigenetic modifications that alter chromatin packing and thereby access of DNA-binding proteins to their DNA sites.
 
We have several lines of research in the laboratory aimed at understanding the role of nuclear signalling in regulating epigenetic modifications and chromatin remodelling in neurons. More recently we discovered a novel class of atypical enhancers linked to the activation of activity-dependent genes in the cortex. 
 
Once a gene is transcribed, its mRNA must be translated into a protein, which then has to be transported to where it is needed.  This transport can be especially challenging in neurons because the nucleus can be very far away from the final location of the protein. The growth cone of a sensory neuron in a mouse embryo, for example, can be millimetres, or even centimetres away from the cell body. Therefore, many mRNAs encoding proteins required for axon growth during development or axonal regeneration after injury must be transported and locally translated in axons.
 
A second line of research in the laboratory is exploring the hypothesis that transcripts located to axons are structurally unique. We discovered that the 3’ untranslated regions of axonal mRNAs undergo local remodelling and cleavage, generating a new class of noncoding RNA with as-of-yet unknown functions.
 
Riccio lab research imageRiccio lab research image

Selected publications

Castillo PE, et al (2023). Presynaptic protein synthesis in brain function and disease. J. Neuroscience; 43(45): 7483-8

Luisier R et al (2023). Axonal mRNA localization in response to neurotrophin treatment. Genome Research 33(9);1497-1512

Brookes E, et al (2022). A novel enhancer that regulates Bdnf expression in developing cortical neurons. iScience, Dec 1;26(1):105695

Andreassi C, et al (2021). Cytoplasmic cleavage of IMPA1 30 UTR is necessary for maintaining axon integrity. Cell Rep 34, 108778

Crerar H, et al (2019). Regulation of NGF signaling by an axonal untranslated mRNA. Neuron, 102 (3), 553-563

Brookes E & Riccio A (2019). Location, location, location: Nuclear structure regulates gene expression in neurons. Current Opinion in Neurobiology, 59:16-25

Riccio A (2018). RNA targeting and translation in axons. Science,359:1331-2

 
 

Funders

Wellcome
European Research Council
Medical Research Council
 

Research themes

Neuronal development
Gene expression
Epigenetics
RNA metabolism
 

Technology

Next generation sequencing
Bioinformatics
Mouse genetics
 

People

Braulio Martinez  (Postdoctoral Fellow)
Marousa Darsinou  (Postdoctoral Fellow)
Emma Lloyd (PhD student)
Hanzhong Bai (LiDo PhD student)
Shiqi Wang (PhD student)
Paraskevi Boulasiki  (Research assistant)
Vera Jing (Undergraduate student)
Linqiao Tian (Undergraduate student)
 
 

Collaborators

Adolfo Saiardi (LMCB, UK)
Jernej Ule (UCL, UK)
Rejji Kuruvilla (Johns Hopkins University, USA)
Paolo Salomoni (DZNE, Germany)
Marco Gaspari (University of Catanzaro School of Medicine, Italy)
Gerhard Schratt (ETH Zurich)
Raphaelle Luisier (Idiap Martigny Switzerland)