Epitranscriptomics: new players in an old game

Area of Science:

• Molecular Biology
• Genetics
• Gerontology

Background:

• Ageing is a complex biological process with poorly understood molecular drivers, despite being a major risk factor for numerous diseases.
• Over 170 chemical RNA modifications, collectively termed the epitranscriptome, regulate RNA metabolism and are increasingly implicated in ageing.
• Dysregulation of the epitranscriptome is linked to age-related diseases and ageing hallmarks in mammals.

Approach:

• This review synthesizes current research on RNA modifications, their regulatory enzymes, and their connection to ageing.
• It explores the potential role of RNA modifications in regulating non-coding RNAs involved in ageing, such as transposable elements and tRNA fragments.
• The review includes a reanalysis of mouse tissue datasets to identify age-related transcriptional changes in RNA modification machinery.

Key Points:

• Mutations in RNA modifying enzymes affect lifespan in model organisms.
• Changes in mRNA modifications and RNA modifier expression are observed with age and in neurodegenerative diseases.
• The epitranscriptome is emerging as a key regulator of ageing and lifespan.

Conclusions:

• RNA modifications and their regulatory enzymes are critical players in the ageing process.
• Understanding the epitranscriptome offers novel therapeutic avenues for age-related diseases.
• Further research into RNA modifications' role in ncRNAs like transposable elements and tRNA fragments is warranted.