ArticleMolecular cell2024
Alternative translation initiation produces synaptic organizer proteoforms with distinct localization and functions.
Article in Molecular cell, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- 5' UTR length shapes alternative N-terminal protein isoforms across cancers and in rare disease.EMBO reports · 2026Article
- Article
- 5' UTR length regulates alternative N-terminal protein isoform production in health and disease.bioRxiv : the preprint server for biology · 2026Article
- c.98 + 3A>G and c.155 + 1G>T splice-site variants in theFrontiers in immunology · 2026Article
- Structural basis for non-AUG translation regulation by 5MPs.bioRxiv : the preprint server for biology · 2025Article
- Alternative Splicing: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- Alternative start codon selection shapes mitochondrial function and rare human diseases.Molecular cell · 2025Article
- The generation and consequences of N-terminal proteoform diversity.Cell reports · 2025Review
- Review
- Ribosome plasticity in glioblastoma: a multi-omics framework for future investigation.Frontiers in genetics · 2025Review
- Where to start? Activity-dependent alternative translation initiation generates multifunctional proteoforms in the brain.Molecular cell · 2024Article
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Abstract
While many mRNAs contain more than one translation initiation site (TIS), the functions of most alternative TISs and their corresponding protein isoforms (proteoforms) remain undetermined. Here, we showed that alternative usage of CUG and AUG TISs in neuronal pentraxin receptor (NPR) mRNA produced two proteoforms, of which the ratio was regulated by RNA secondary structure and neuronal activity. Downstream AUG initiation truncated the N-terminal transmembrane domain and produced a secreted NPR proteoform sufficient in promoting synaptic clustering of AMPA-type glutamate receptors. Mutations that altered the ratio of NPR proteoforms reduced AMPA receptors in parvalbumin-positive interneurons and affected learning behaviors in mice. In addition to NPR, upstream AUU-initiated N-terminal extension of C1q-like synaptic organizers anchored these otherwise secreted factors to the membrane. Together, these results uncovered the plasticity of N-terminal signal sequences regulated by alternative TIS usage as a potentially widespread mechanism in diversifying protein localization and functions.
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