Neural Isoforms of Agrin Are Generated by Reduced PTBP1-RNA Interaction Network Spanning the Neuron-Specific Splicing Regions in AGRN.

ABSTRACT: Agrin is a heparan sulfate proteoglycan essential for the clustering of acetylcholine receptors at the neuromuscular junction. Neuron-specific isoforms of agrin are generated by alternative inclusion of three exons, called Y, Z8, and Z11 exons, although their processing mechanisms remain elusive. We found, by inspection of splicing cis-elements into the human AGRN gene, that binding sites for polypyrimidine tract binding protein 1 (PTBP1) were extensively enriched around Y and Z exons. PTBP1-silencing enhanced the coordinated inclusion of Y and Z exons in human SH-SY5Y neuronal cells, even though three constitutive exons are flanked by these alternative exons. Deletion analysis using minigenes identified five PTBP1-binding sites with remarkable splicing repression acti

SUBMITTER: Bushra S 

PROVIDER: S-EPMC10139058 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature