A comprehensive understanding of molecular changes during brain aging is essential to mitigate cognitive decline and delay neurodegenerative diseases. The interpretation of mRNA alterations during brain aging is influenced by the health and age of the animal cohorts studied. Here, we carefully consider these factors and provide an in-depth investigation of mRNA splicing and dynamics in the aging mouse brain, combining short- and long-read sequencing technologies with extensive bioinformatic analyses. Our findings encompass a spectrum of age-related changes, including differences in isoform usage, decreased mRNA dynamics and a module showing increased expression of neuronal genes. Notably, our results indicate a reduced abundance of mRNA isoforms leading to nonsense-mediated RNA decay and suggest a regulatory role for RNA-binding proteins, indicating that their regulation may be altered leading to the reshaping of the aged brain transcriptome. Collectively, our study highlights the importance of studying mRNA splicing events during brain aging.

Kumar, N., Kluever, V., Barth, E., Krautwurst, S., Furlan, M., Pelizzola, M., et al. (2024). Comprehensive transcriptome analysis reveals altered mRNA splicing and post-transcriptional changes in the aged mouse brain. NUCLEIC ACIDS RESEARCH, 52(6), 2865-2885 [10.1093/nar/gkae172].

Comprehensive transcriptome analysis reveals altered mRNA splicing and post-transcriptional changes in the aged mouse brain

Pelizzola, M;
2024

Abstract

A comprehensive understanding of molecular changes during brain aging is essential to mitigate cognitive decline and delay neurodegenerative diseases. The interpretation of mRNA alterations during brain aging is influenced by the health and age of the animal cohorts studied. Here, we carefully consider these factors and provide an in-depth investigation of mRNA splicing and dynamics in the aging mouse brain, combining short- and long-read sequencing technologies with extensive bioinformatic analyses. Our findings encompass a spectrum of age-related changes, including differences in isoform usage, decreased mRNA dynamics and a module showing increased expression of neuronal genes. Notably, our results indicate a reduced abundance of mRNA isoforms leading to nonsense-mediated RNA decay and suggest a regulatory role for RNA-binding proteins, indicating that their regulation may be altered leading to the reshaping of the aged brain transcriptome. Collectively, our study highlights the importance of studying mRNA splicing events during brain aging.
Articolo in rivista - Articolo scientifico
aging, RNA dynamics, RNA splicing
English
12-mar-2024
2024
52
6
2865
2885
open
Kumar, N., Kluever, V., Barth, E., Krautwurst, S., Furlan, M., Pelizzola, M., et al. (2024). Comprehensive transcriptome analysis reveals altered mRNA splicing and post-transcriptional changes in the aged mouse brain. NUCLEIC ACIDS RESEARCH, 52(6), 2865-2885 [10.1093/nar/gkae172].
File in questo prodotto:
File Dimensione Formato  
Kumar-2024-Nucleic Acid Res-VoR.pdf

accesso aperto

Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Licenza: Creative Commons
Dimensione 3.42 MB
Formato Adobe PDF
3.42 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/467898
Citazioni
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
Social impact