RAN translation
Cellular process
Repeat Associated Non-AUG translation, or RAN translation, is an irregular mode of mRNA translation that can occur in eukaryotic cells.[1][2]
Mechanism
For the majority of eukaryotic messenger RNAs (mRNAs), translation initiates from a methionine-encoding AUG start codon following the molecular processes of 'cap-binding' and 'scanning' by ribosomal pre-initiation complexes (PICs). In rare exceptions, such as translation by viral IRES-containing mRNAs, 'cap-binding' and/or 'scanning' are not required for initiation, although AUG is still typically used as the first codon. RAN translation is an exception to the canonical rules as it uses variable start site selection and initiates from a non-AUG codon, but may still depend on 'cap-binding' and 'scanning'.[3]
Disease
RAN translation produces a variety of dipeptide repeat proteins by translation of expanded hexanucleotide repeats present in an intron of the C9orf72 gene. The expansion of the hexanucleotide repeats and thus accumulation of dipeptide repeat proteins are thought to cause cellular toxicity that leads to neurodegeneration in ALS disease.[4][5][6][7][8][9]
See also
- Trinucleotide repeat disorder
- Eukaryotic translation
- C9orf72
References
- ^ Zu, T.; Gibbens, B.; Doty, N. S.; Gomes-Pereira, M.; Huguet, A.; Stone, M. D.; Margolis, J.; Peterson, M.; Markowski, T. W.; Ingram, M. A. C.; Nan, Z.; Forster, C.; Low, W. C.; Schoser, B.; Somia, N. V.; Clark, H. B.; Schmechel, S.; Bitterman, P. B.; Gourdon, G.; Swanson, M. S.; Moseley, M.; Ranum, L. P. W. (2010). "Non-ATG-initiated translation directed by microsatellite expansions". Proceedings of the National Academy of Sciences. 108 (1): 260–265. doi:10.1073/pnas.1013343108. ISSN 0027-8424. PMC 3017129. PMID 21173221.
- ^ Copenhaver, Gregory P.; Pearson, Christopher E. (2011). "Repeat Associated Non-ATG Translation Initiation: One DNA, Two Transcripts, Seven Reading Frames, Potentially Nine Toxic Entities!". PLOS Genetics. 7 (3): e1002018. doi:10.1371/journal.pgen.1002018. ISSN 1553-7404. PMC 3053344. PMID 21423665.
- ^ Cox, Diana C.; Cooper, Thomas A. (2016). "Non-canonical RAN Translation of CGG Repeats Has Canonical Requirements". Molecular Cell. 62 (2): 155–156. doi:10.1016/j.molcel.2016.04.004. ISSN 1097-2765. PMID 27105111.
- ^ Renoux, Abigail J.; Todd, Peter K. (2012). "Neurodegeneration the RNA way". Progress in Neurobiology. 97 (2): 173–189. doi:10.1016/j.pneurobio.2011.10.006. ISSN 0301-0082. PMC 3582174. PMID 22079416.
- ^ Strzyz, Paulina (2016). "Translation: The features of pathologic RAN translation". Nature Reviews Molecular Cell Biology. 17 (5): 264. doi:10.1038/nrm.2016.52. ISSN 1471-0072. S2CID 41908729.
- ^ Bañez-Coronel, Monica; Ayhan, Fatma; Tarabochia, Alex D.; Zu, Tao; Perez, Barbara A.; Tusi, Solaleh Khoramian; Pletnikova, Olga; Borchelt, David R.; Ross, Christopher A.; Margolis, Russell L.; Yachnis, Anthony T.; Troncoso, Juan C.; Ranum, Laura P.W. (2015). "RAN Translation in Huntington Disease". Neuron. 88 (4): 667–677. doi:10.1016/j.neuron.2015.10.038. ISSN 0896-6273. PMC 4684947. PMID 26590344.
- ^ Kearse, Michael G.; Green, Katelyn M.; Krans, Amy; Rodriguez, Caitlin M.; Linsalata, Alexander E.; Goldstrohm, Aaron C.; Todd, Peter K. (2016). "CGG Repeat-Associated Non-AUG Translation Utilizes a Cap-Dependent Scanning Mechanism of Initiation to Produce Toxic Proteins". Molecular Cell. 62 (2): 314–322. doi:10.1016/j.molcel.2016.02.034. ISSN 1097-2765. PMC 4854189. PMID 27041225.
- ^ Green, Katelyn M.; Linsalata, Alexander E.; Todd, Peter K. (2016). "RAN translation—What makes it run?". Brain Research. 1647: 30–42. doi:10.1016/j.brainres.2016.04.003. ISSN 0006-8993. PMC 5003667. PMID 27060770.
- ^ Mori, K.; Weng, S.-M.; Arzberger, T.; May, S.; Rentzsch, K.; Kremmer, E.; Schmid, B.; Kretzschmar, H. A.; Cruts, M.; Van Broeckhoven, C.; Haass, C.; Edbauer, D. (2013). "The C9orf72 GGGGCC Repeat Is Translated into Aggregating Dipeptide-Repeat Proteins in FTLD/ALS". Science. 339 (6125): 1335–1338. Bibcode:2013Sci...339.1335M. doi:10.1126/science.1232927. ISSN 0036-8075. PMID 23393093. S2CID 32244381.
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Gene expression
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