Laboratory Valérie Hilgers

Laboratory Valérie Hilgers

RNA Processing in the nervous system

We investigate the molecular mechanisms underlying neuron-specific RNA signatures. We also aim to understand how RNA processing affects neuronal development and function.

The nervous system is composed of highly polarized cells of complex and dynamic architecture. The formation and maintenance of neurons and neural circuits require the coordinated expression of genes at each step of RNA metabolism: from transcription, processing, localized transport and translation, to degradation. To achieve this level of complexity, neurons employ mechanisms that increase RNA regulatory potential: alternative splicing, alternative polyadenylation, and non-coding RNA expression.

Goals

The extent of neuronal RNA diversity, and the astounding number of mRNA isoforms and non-coding RNAs present in neurons, have only been appreciated in recent years with the emergence of new transcriptomics technologies. Our long-term goal is to gain an understanding of the neuron-specific RNA landscape that drives neural function in health and disease. 

Approach

We are interested in the transcriptional and co-transcriptional mechanisms that lead to the emergence of neuronal RNA signatures in the nucleus. We also study the post-transcriptional regulation of these RNAs in the cytoplasm, and their role in neuronal development and function.

We use Drosophila melanogaster as a model system. Our technologies range from functional genetics, behavior studies, and imaging, to RNA biochemistry. We have a special focus on brain transcriptomics, including iCLIP, 3’-seq, RNA-seq, and ultra-long-read sequencing.

Impact

Neuron-specific RNA processing also occurs in humans; mechanistic and functional insight is lacking, especially from animal models. This topic is of particular interest since neural RNA regulation has emerged as a crucial contributing factor in neurological diseases.  


Selected Publications

1.
Carrasco J, Rauer M, Hummel B, Grzejda D, Alfonso-Gonzalez C, Lee Y, Wang Q, Puchalska M, Mittler G, Hilgers V (2020)
ELAV and FNE Determine Neuronal Transcript Signatures through EXon-Activated Rescue
Molecular Cell (80), 156-163.
2.
Hilgers V (2015)
Alternative polyadenylation coupled to transcription initiation: Insights from ELAV-mediated 3’ UTR extension
RNA Biology 12, 918-921 (Review article).
3.
Oktaba K, Zhang W, Lotz TS, Jun DJ, Lemke SB, Ng SP, Esposito E, Levine M*, Hilgers V* (2015)
ELAV links paused Pol II to alternative polyadenylation in the Drosophila nervous system
Molecular Cell 57, 341-348.

*corresponding authors
4.
Hilgers V, Lemke SB, Levine M (2012)
ELAV mediates 3’ UTR extension in the Drosophila nervous system
Genes and Development 26, 2259-2264.
5.
Hilgers V, Perry MW, Hendrix D, Stark A, Levine M, Haley B (2011)
Neural-specific elongation of 3’ UTRs during Drosophila development
Proceedings of the National Academy of Sciences 108, 15864-15869.
6.
Hilgers V, Bushati N, Cohen SM (2010)
Drosophila microRNAs 263a/b confer robustness during development by protecting nascent sense organs from apoptosis
PLoS Biology 8, e100039.

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