El CRAI romandrà tancat del 24 de desembre de 2025 al 6 de gener de 2026. La validació de documents es reprendrà a partir del 7 de gener de 2026.
El CRAI permanecerá cerrado del 24 de diciembre de 2025 al 6 de enero de 2026. La validación de documentos se reanudará a partir del 7 de enero de 2026.
From 2025-12-24 to 2026-01-06, the CRAI remain closed and the documents will be validated from 2026-01-07.
 
Miniatura

Fitxers

s41598-021-83152-w.pdf (10.36 MB)

Tipus de document

Article

Versió

Versió publicada

Data de publicació

2021-02-11

Llicència de publicació

cc by (c) Biayna et al., 2021
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/176673

Using antisense oligonucleotides for the physiological modulation of the alternative splicing of NF1 exon 23a during PC12 neuronal differentiation

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1038/s41598-021-83152-w

Resum

Neurofibromatosis Type 1 (NF1) is a genetic condition affecting approximately 1:3500 persons worldwide. The NF1 gene codes for neurofibromin protein, a GTPase activating protein (GAP) and a negative regulator of RAS. The NF1 gene undergoes alternative splicing of exon 23a (E23a) that codes for 21 amino acids placed at the center of the GAP related domain (GRD). E23a-containing type II neurofibromin exhibits a weaker Ras-GAP activity compared to E23a-less type I isoform. Exon E23a has been related with the cognitive impairment present in NF1 individuals. We designed antisense Phosphorodiamidate Morpholino Oligomers (PMOs) to modulate E23a alternative splicing at physiological conditions of gene expression and tested their impact during PC12 cell line neuronal differentiation. Results show that any dynamic modification of the natural ratio between type I and type II isoforms disturbed neuronal differentiation, altering the proper formation of neurites and deregulating both the MAPK/ERK and cAMP/PKA signaling pathways. Our results suggest an opposite regulation of these pathways by neurofibromin and the possible existence of a feedback loop sensing neurofibromin-related signaling. The present work illustrates the utility of PMOs to study alternative splicing that could be applied to other alternatively spliced genes in vitro and in vivo.

Matèries

Neurofibromatosi, Oligonucleòtids

Matèries (anglès)

Neurofibromatosis, Oligonucleotides

Citació

Col·leccions

Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

BIAYNA, Josep, MAZUELAS, Helena, GEL MORENO, Bernat, TERRIBAS, Ernest, DUMBOVIC, Gabrijela, ROSAS, Inma, FERNÁNDEZ RODRÍGUEZ, Juana, BLANCO GUILLERMO, Ignacio, CASTELLANOS, Elisabeth, CARRIÓ, Meritxell, LÁZARO GARCÍA, Conxi, SERRA ARENAS, Eduard. Using antisense oligonucleotides for the physiological modulation of the alternative splicing of NF1 exon 23a during PC12 neuronal differentiation. _Scientific Reports_. 2021. Vol. 11. [consulta: 7 de gener de 2026]. [Disponible a: https://hdl.handle.net/2445/176673]

Exportar metadades

JSON - METS

Compartir registre