mRNA stability in soma and neurites of cultured neuronal cells

Abstract

Neurons rely on mRNA localization and local protein synthesis in neurites to regulate synaptic plasticity, axonogenesis and neural signaling. The local regulation of mRNA stability in neurites is poorly understood. To determine mRNA decay rates, we analyzed the subcellular transcriptomes of neural projections and soma of mouse neuronal cells following inhibition of transcription with actinomycin-D. Less stable transcripts were enriched for GU-rich elements in their 3' UTRs. Around 12% of alternative splicing isoform pairs differed in stability, and cassette alternative ("skipped") exons that negatively impact stability are enriched for A-rich sequences. Overall, decay rates were similar across soma and neurites. However, differences in stability between soma and neurites were observed for GC-rich alternative first exon isoforms, which were preferentially stabilized in neurites. Our results suggest that 5' UTRs may play a key role in regulating local mRNA stability in neurites.