TY  - JOUR
A1  - Luisier, Raphaëlle
A1  - Andreassi, Catia
A1  - Fournier, Lisa
A1  - Riccio, Antonella
T1  - The predicted RNA-binding protein regulome of axonal mRNAs
Y1  - 2023/09/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1497 
EP  - 1512 
DO  - 10.1101/gr.277804.123 
VL  - 33 
IS  - 9 
UR  - http://genome.cshlp.org/content/33/9/1497.abstract 
N2  - Neurons are morphologically complex cells that rely on the compartmentalization of protein expression to develop and maintain their cytoarchitecture. The targeting of RNA transcripts to axons is one of the mechanisms that allows rapid local translation of proteins in response to extracellular signals. 3′ Untranslated regions (UTRs) of mRNA are noncoding sequences that play a critical role in determining transcript localization and translation by interacting with specific RNA-binding proteins (RBPs). However, how 3′ UTRs contribute to mRNA metabolism and the nature of RBP complexes responsible for these functions remains elusive. We performed 3′ end sequencing of RNA isolated from cell bodies and axons of sympathetic neurons exposed to either nerve growth factor (NGF) or neurotrophin 3 (NTF3, also known as NT-3). NGF and NTF3 are growth factors essential for sympathetic neuron development through distinct signaling mechanisms. Whereas NTF3 acts mostly locally, NGF signal is retrogradely transported from axons to cell bodies. We discovered that both NGF and NTF3 affect transcription and alternative polyadenylation in the nucleus and induce the localization of specific 3′ UTR isoforms to axons, including short 3′ UTR isoforms found exclusively in axons. The integration of our data with CLIP sequencing data supports a model whereby long 3′ UTR isoforms associate with RBP complexes in the nucleus and, upon reaching the axons, are remodeled locally into shorter isoforms. Our findings shed new light into the complex relationship between nuclear polyadenylation, mRNA localization, and local 3′ UTR remodeling in developing neurons. 
ER  -