A post-transcriptional regulatory landscape of aging in the female mouse hippocampus

Frontiers in Aging Neuroscience

Aging Neuroscience

Raphaelle Winsky-Sommerer¹  Valentina Iadevaia¹  Carla Möller-Levet¹  Helen A. King¹  André P. Gerber² 

[1] Faculty of Health and Medical Sciences, School of Biosciences and Medicine, University of Surrey, Guildford, Surrey, United Kingdom;null;

关键词: brain;    translatome;    transcriptome;    alternative splicing;    RNA-binding protein;    Polysome analysis;    mitochondria;    polyadenylation;   

DOI  :  10.3389/fnagi.2023.1119873

 received in 2022-12-09, accepted in 2023-02-27,  发布年份 2023

来源: Frontiers

【 摘 要 】

Aging is associated with substantial physiological changes and constitutes a major risk factor for neurological disorders including dementia. Alterations in gene expression upon aging have been extensively studied; however, an in-depth characterization of post-transcriptional regulatory events remains elusive. Here, we profiled the age-related changes of the transcriptome and translatome in the female mouse hippocampus by RNA sequencing of total RNA and polysome preparations at four ages (3-, 6-, 12-, 20-month-old); and we implemented a variety of bioinformatics approaches to unravel alterations in transcript abundance, alternative splicing, and polyadenylation site selection. We observed mostly well-coordinated transcriptome and translatome expression signatures across age including upregulation of transcripts related to immune system processes and neuroinflammation, though transcripts encoding ribonucleoproteins or associated with mitochondrial functions, calcium signaling and the cell-cycle displayed substantial discordant profiles, suggesting translational control associated with age-related deficits in hippocampal-dependent behavior. By contrast, alternative splicing was less preserved, increased with age and was associated with distinct functionally-related transcripts encoding proteins acting at synapses/dendrites, RNA-binding proteins; thereby predicting regulatory roles for RBM3 and CIRBP. Only minor changes in polyadenylation site selection were identified, indicating pivotal 3′-end selection in young adults compared to older groups. Overall, our study provides a comprehensive resource of age-associated post-transcriptional regulatory events in the mouse hippocampus, enabling further examination of the molecular features underlying age-associated neurological diseases.

【 授权许可】

Unknown   
Copyright © 2023 Winsky-Sommerer, King, Iadevaia, Möller-Levet and Gerber.