Team photo Hilgers Lab

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.


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. 


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.


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

Alfonso-Gonzalez C, Legnini I, Holec S, Arrigoni L, Ozbulut HC, Mateos F, Koppstein D, Rybak-Wolf A Bönisch U, Rajewsky N and Hilgers V (2023)
Sites of transcription initiation drive mRNA isoform selection.
Cell 186 (11), 2438-2455.e22
Grzejda D, Mach J, Schweizer JA, Hummel B, Rezansoff AM, Eggenhofer F, Panhale A, Lalioti ME, Cabezas Wallscheid N, Backofen R, Felsenberg J & Hilgers V (2022)
The long noncoding RNA mimi scaffolds neuronal granules to maintain nervous system maturity
Science Advances 8(39): eabo5578.
Hilgers, V (2022)
Regulation of neuronal RNA signatures by ELAV/Hu proteins
Wiley interdisciplinary reviews: WIREs RNA, e1733.
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.
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

More publications

Go to Editor View