Group Leader

Dr. Valérie Hilgers
Dr. Valérie Hilgers
Group Leader

Lab Valérie Hilgers

Laboratory Valérie Hilgers

Mechanism of RNA processing in neurons

Another aim of our lab is to elucidate the mechanism of neuron-specific 3’ UTR extension. This unique type of alternative 3’ processing is mediated by the RNA-binding protein ELAV, that binds to newly transcribed polyadenylation sites and inhibits polyadenylation.

ELAV-mediated 3’ UTR extension is regulated at transcription initiation ChIP-Seq metadata show that ELAV and paused Pol II are found at promoter regions of genes that undergo 3’ UTR extension. Model: In neurons, ELAV associates with the promoter region of its target genes, which is usually engaged by paused Pol II. During transcription, ELAV binds to the nascent transcript in the vicinity of each proximal polyadenylation site. The inhibition of cleavage and polyadenylation (CPA) at proximal sites causes transcriptional read-through and formation of an extended 3’ UTR. Zoom Image

ELAV-mediated 3’ UTR extension is regulated at transcription initiation

ChIP-Seq metadata show that ELAV and paused Pol II are found at promoter regions of genes that undergo 3’ UTR extension. Model: In neurons, ELAV associates with the promoter region of its target genes, which is usually engaged by paused Pol II. During transcription, ELAV binds to the nascent transcript in the vicinity of each proximal polyadenylation site. The inhibition of cleavage and polyadenylation (CPA) at proximal sites causes transcriptional read-through and formation of an extended 3’ UTR.

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Our previous work uncovered an unexpected link between transcription initiation and alternative mRNA processing: ELAV binds to promoter regions of its target genes, and this association is facilitated by promoter-proximal RNA Polymerase II (Pol II) pausing. How ELAV at transcription initiation affects RNA processing many kilobases downstream remains mysterious. We are studying how epigenetic marks, promoter sequence, and Pol II pausing cooperate to promote neural-specific mRNA extension. Methodologies include whole-genome approaches such as ChIP and iCLIP, proteomics as well as RNA biochemistry and functional genetics. 

 
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