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Journal article
Localized IRES-Dependent Translation of ER Chaperone Protein mRNA in Sensory Axons
PloS one, v 7(7), 40788
24 Jul 2012
PMID: 22911708
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Transport of neuronal mRNAs into distal nerve terminals and growth cones allows axonal processes to generate proteins autonomous from the cell body. While the mechanisms for targeting mRNAs for transport into axons has received much attention, how specificity is provided to the localized translational apparatus remains largely unknown. In other cellular systems, protein synthesis can be regulated by both cap-dependent and cap-independent mechanisms. The possibility that these mechanisms are used by axons has not been tested. Here, we have used expression constructs encoding axonally targeted bicistronic reporter mRNAs to determine if sensory axons can translate mRNAs through cap-independent mechanisms. Our data show that the well-defined IRES element of encephalomyocarditis virus (EMCV) can drive internal translational initiation of a bicistronic reporter mRNA in distal DRG axons. To test the potential for cap-independent translation of cellular mRNAs, we asked if calreticulin or grp78/BiP mRNA 59UTRs might have IRES activity in axons. Only grp78/BiP mRNA 5'UTR showed clear IRES activity in axons when placed between the open reading frames of diffusion limited fluorescent reporters. Indeed, calreticulin's 5'UTR provided an excellent control for potential read through by ribosomes, since there was no evidence of internal initiation when this UTR was placed between reporter ORFs in a bicistronic mRNA. This study shows that axons have the capacity to translate through internal ribosome entry sites, but a simple binary choice between cap-dependent and cap-independent translation cannot explain the specificity for translation of individual mRNAs in distal axons.
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Details
- Title
- Localized IRES-Dependent Translation of ER Chaperone Protein mRNA in Sensory Axons
- Creators
- Almudena Pacheco - Drexel UniversityJeffery L. Twiss - Drexel University
- Publication Details
- PloS one, v 7(7), 40788
- Publisher
- Public Library Science
- Number of pages
- 10
- Grant note
- R01-NS041596 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01NS041596 / NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS) Miriam and Sheldon F. Aldelson Medical Research Foundation
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000306751300014
- Scopus ID
- 2-s2.0-84864193014
- Other Identifier
- 991021892010904721
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- Web of Science research areas
- Biochemistry & Molecular Biology