ArticlePloS one2014
A non-canonical initiation site is required for efficient translation of the dendritically localized Shank1 mRNA.
Article in PloS one, 2014. 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, 27 citations in OpenAlex.
- Heimdall, an alternative protein issued from a ncRNA related to kappa light chain variable region of immunoglobulins from astrocytes: a new player in neural proteome.Cell death & disease · 2023Article
- Tandem repeats ubiquitously flank and contribute to translation initiation sites.BMC genomic data · 2022Article
- LncRNAs and Chromatin Modifications Pattern mFrontiers in genetics · 2022Review
- Alternative Splicing of the Delta-Opioid Receptor Gene Suggests Existence of New Functional Isoforms.Molecular neurobiology · 2019Article
- Cell-Type-Specific Profiling of Alternative Translation Identifies Regulated Protein Isoform Variation in the Mouse Brain.Cell reports · 2019Article
- Kinases of eIF2a Switch Translation of mRNA Subset during Neuronal Plasticity.International journal of molecular sciences · 2017Review
- Ribosomal selection of mRNAs with degenerate initiation triplets.Nucleic acids research · 2017Article
- Proteomics of the Synapse--A Quantitative Approach to Neuronal Plasticity.Molecular & cellular proteomics : MCP · 2016Review
- Upstream Open Reading Frames Located in the Leader of Protein Kinase Mζ mRNA Regulate Its Translation.Frontiers in molecular neuroscience · 2016Article
- Proteogenomic Analysis Identifies a Novel Human SHANK3 Isoform.International journal of molecular sciences · 2015Article
- To Know How a Gene Works, We Need to Redefine It First but then, More Importantly, to Let the Cell Itself Decide How to Transcribe and Process Its RNAs.International journal of biological sciences · 2015Review
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Local protein synthesis in dendrites enables neurons to selectively change the protein complement of individual postsynaptic sites. Though it is generally assumed that this mechanism requires tight translational control of dendritically transported mRNAs, it is unclear how translation of dendritic mRNAs is regulated. We have analyzed here translational control elements of the dendritically localized mRNA coding for the postsynaptic scaffold protein Shank1. In its 5' region, the human Shank1 mRNA exhibits two alternative translation initiation sites (AUG⁺¹ and AUG⁺²¹⁴), three canonical upstream open reading frames (uORFs1-3) and a high GC content. In reporter assays, fragments of the 5'UTR with high GC content inhibit translation, suggesting a contribution of secondary structures. uORF3 is most relevant to translation control as it overlaps with the first in frame start codon (AUG⁺¹), directing translation initiation to the second in frame start codon (AUG⁺²¹⁴). Surprisingly, our analysis points to an additional uORF initiated at a non-canonical ACG start codon. Mutation of this start site leads to an almost complete loss of translation initiation at AUG⁺¹, demonstrating that this unconventional uORF is required for Shank1 synthesis. Our data identify a novel mechanism whereby initiation at a non-canonical site allows for translation of the main Shank1 ORF despite a highly structured 5'UTR.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.