RAN translation

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Repeat Associated Non-AUG translation, or RAN translation, is an irregular mode of mRNA translation that can occur in eukaryotic cells. [1] [2]

Contents

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

References

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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.
  9. ↑ 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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