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Activity-dependent ribosome profiling reveals the landscape of canonical and non-canonical translation in brain tissue

ABSTRACT: Neural activity-dependent translation is essential for synaptic plasticity and diverse brain functions. Translation involves not only canonical main open reading frames (mORFs) but also upstream ORFs (uORFs), which may regulate mORF expression. However, due to technical limitations, systematic investigation of activity-dependent uORFs and mORFs in brain tissues remains challenging. Here, we developed a ribosome tagging and purification strategy that bypasses the prolonged turnover of ribosomal proteins, enabling ribosome profiling with one-hour temporal resolution after neural stimulation. Applying this strategy to mouse hippocampal slices undergoing long-term potentiation, we identified hundreds of activity-induced mORFs and uORFs, a subset of which served as robust markers for activity status. Notably, ~22% of the upregulated uORFs overlapped with those induced by the integrated stress response, suggesting potential crosstalk between these signaling pathways. This study provides a useful technique and resources for deciphering molecular mechanisms underlying activity and translation-dependent brain functions in health and disease.

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Motomasa Tanaka

PROVIDER: PXD074666 | JPOST Repository | Mon May 25 00:00:00 GMT+01:00 2026

REPOSITORIES: jPOST

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			Action	DRS
	20251112_EC_KT_EC_Flagx3-Egr1_uORF_w_cLTP_1.raw	Raw
	20251112_EC_KT_EC_Flagx3-Egr1_uORF_w_cLTP_2.raw	Raw
	20251112_EC_KT_EC_Flagx3-Egr1_uORF_w_cLTP_3.raw	Raw
	20251112_EC_KT_EC_Flagx3-Egr1_uORF_wo_cLTP_1.raw	Raw
	20251112_EC_KT_EC_Flagx3-Egr1_uORF_wo_cLTP_2.raw	Raw

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