Pluto Bioinformatics

GSE97461: TRAP sequencing of D1 and D2 spiny projection neurons from young and old mice

Bulk RNA sequencing

The aging brain encounters various cellular, molecular, and metabolic changes, which can differentially impact neuronal cell types and regions. Here, we describe the age- and brain region-specific accumulation of ribosome-bound mRNA fragments consisting of transcript 3' untranslated regions (UTRs), without the 5'UTR and open reading frame. This phenomenon impacts hundreds of genes in aged D1 spiny projection neurons of the mouse striatum and occurs throughout the human brain, particularly in more metabolically active nuclei. Isolated 3'UTRs can be triggered by oxidative stress. We present evidence that oxidative stress-induced impairment of the iron-sulfur-containing ribosome recycling factor ABCE1 triggers ribosome stalling and mRNA cleavage by the No-Go decay pathway, yielding 3'UTR fragments protected by 5'-stalled ribosomes. Isolated 3'UTRs are a hallmark of the aging brain, potentially contributing to cell- and region-specific phenotypes. SOURCE: Peter Sudmant MIT