RNA imbalance as a hallmark of cellular ageing.

Abstract

Major advances over the past few decades have highlighted the complex regulation of RNA from transcription to nuclear export and from translation to decay. Despite the emerging cellular landscape of malleable and multifunctional RNA molecules, the role of RNA dysregulation in ageing, one of the most fundamental processes of human biology, is underappreciated. Here we focus on ageing-linked dysregulation of the mRNA life cycle. We summarize how RNA metabolism steadily deviates throughout ageing and senescence: in transcription, aged cells bias shorter genes at the expense of complex transcripts; in splicing, ageing-linked alternative exon usage is common; in translation, ribosomal collisions on mRNAs decouple transcriptional output from protein production; and in decay, aberrant RNAs accumulate due to poor degradation activity. We close by discussing how ageing-linked dysregulation of RNA biology can drive cellular stress and thus serve as a therapeutic target to reverse disease.