RAN translation

{{Short description|Irregular mRNA translation}} '''R'''epeat '''A'''ssociated '''N'''on-AUG translation, or '''RAN translation''', is an irregular mode of mRNA translation that can occur in eukaryotic cells.<ref name="ZuGibbens2010">{{cite journal|last1=Zu|first1=T.|last2=Gibbens|first2=B.|last3=Doty|first3=N. S.|last4=Gomes-Pereira|first4=M.|last5=Huguet|first5=A.|last6=Stone|first6=M. D.|last7=Margolis|first7=J.|last8=Peterson|first8=M.|last9=Markowski|first9=T. W.|last10=Ingram|first10=M. A. C.|last11=Nan|first11=Z.|last12=Forster|first12=C.|last13=Low|first13=W. C.|last14=Schoser|first14=B.|last15=Somia|first15=N. V.|last16=Clark|first16=H. B.|last17=Schmechel|first17=S.|last18=Bitterman|first18=P. B.|last19=Gourdon|first19=G.|last20=Swanson|first20=M. S.|last21=Moseley|first21=M.|last22=Ranum|first22=L. P. W.|title=Non-ATG-initiated translation directed by microsatellite expansions|journal=Proceedings of the National Academy of Sciences|volume=108|issue=1|year=2010|pages=260–265|issn=0027-8424|doi=10.1073/pnas.1013343108|pmid=21173221|pmc=3017129|doi-access=free}}</ref><ref name="CopenhaverPearson2011">{{cite journal|last1=Copenhaver|first1=Gregory P.|last2=Pearson|first2=Christopher E.|title=Repeat Associated Non-ATG Translation Initiation: One DNA, Two Transcripts, Seven Reading Frames, Potentially Nine Toxic Entities!|journal=PLOS Genetics|volume=7|issue=3|year=2011|article-number=e1002018|issn=1553-7404|doi=10.1371/journal.pgen.1002018|pmid=21423665|pmc=3053344 |doi-access=free }}</ref>

== 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'.<ref name="CoxCooper2016">{{cite journal|last1=Cox|first1=Diana C.|last2=Cooper|first2=Thomas A.|title=Non-canonical RAN Translation of CGG Repeats Has Canonical Requirements|journal=Molecular Cell|volume=62|issue=2|year=2016|pages=155–156|issn=1097-2765|doi=10.1016/j.molcel.2016.04.004|pmid=27105111|doi-access=free}}</ref>

== 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.<ref name="RenouxTodd2012">{{cite journal|last1=Renoux|first1=Abigail J.|last2=Todd|first2=Peter K.|title=Neurodegeneration the RNA way|journal=Progress in Neurobiology|volume=97|issue=2|year=2012|pages=173–189|issn=0301-0082|doi=10.1016/j.pneurobio.2011.10.006|pmid=22079416|pmc=3582174}}</ref><ref name="Strzyz2016">{{cite journal|last1=Strzyz|first1=Paulina|title=Translation: The features of pathologic RAN translation|journal=Nature Reviews Molecular Cell Biology|volume=17|issue=5|year=2016|page=264|issn=1471-0072|doi=10.1038/nrm.2016.52|s2cid=41908729|doi-access=free}}</ref><ref name="Bañez-CoronelAyhan2015">{{cite journal|last1=Bañez-Coronel|first1=Monica|last2=Ayhan|first2=Fatma|last3=Tarabochia|first3=Alex D.|last4=Zu|first4=Tao|last5=Perez|first5=Barbara A.|last6=Tusi|first6=Solaleh Khoramian|last7=Pletnikova|first7=Olga|last8=Borchelt|first8=David R.|last9=Ross|first9=Christopher A.|last10=Margolis|first10=Russell L.|last11=Yachnis|first11=Anthony T.|last12=Troncoso|first12=Juan C.|last13=Ranum|first13=Laura P.W.|title=RAN Translation in Huntington Disease|journal=Neuron|volume=88|issue=4|year=2015|pages=667–677|issn=0896-6273|doi=10.1016/j.neuron.2015.10.038|pmid=26590344|pmc=4684947}}</ref><ref name="KearseGreen2016">{{cite journal|last1=Kearse|first1=Michael G.|last2=Green|first2=Katelyn M.|last3=Krans|first3=Amy|last4=Rodriguez|first4=Caitlin M.|last5=Linsalata|first5=Alexander E.|last6=Goldstrohm|first6=Aaron C.|last7=Todd|first7=Peter K.|title=CGG Repeat-Associated Non-AUG Translation Utilizes a Cap-Dependent Scanning Mechanism of Initiation to Produce Toxic Proteins|journal=Molecular Cell|volume=62|issue=2|year=2016|pages=314–322|issn=1097-2765|doi=10.1016/j.molcel.2016.02.034|pmid=27041225|pmc=4854189}}</ref><ref name="GreenLinsalata2016">{{cite journal|last1=Green|first1=Katelyn M.|last2=Linsalata|first2=Alexander E.|last3=Todd|first3=Peter K.|title=RAN translation—What makes it run?|journal=Brain Research|volume=1647|year=2016|pages=30–42|issn=0006-8993|doi=10.1016/j.brainres.2016.04.003|pmid=27060770|pmc=5003667}}</ref><ref name="MoriWeng2013">{{cite journal|last1=Mori|first1=K.|last2=Weng|first2=S.-M.|last3=Arzberger|first3=T.|last4=May|first4=S.|last5=Rentzsch|first5=K.|last6=Kremmer|first6=E.|last7=Schmid|first7=B.|last8=Kretzschmar|first8=H. A.|last9=Cruts|first9=M.|last10=Van Broeckhoven|first10=C.|last11=Haass|first11=C.|last12=Edbauer|first12=D.|title=The C9orf72 GGGGCC Repeat Is Translated into Aggregating Dipeptide-Repeat Proteins in FTLD/ALS|journal=Science|volume=339|issue=6125|year=2013|pages=1335–1338|issn=0036-8075|doi=10.1126/science.1232927|pmid=23393093|bibcode=2013Sci...339.1335M|s2cid=32244381|doi-access=free}}</ref>

== References ==

Category:Protein biosynthesis Category:Molecular biology Category:Gene expression Category:Protein complexes Category:RNA-binding proteins

Category:Biochemistry Category:RNA Category:Proteins Category:Neurodegenerative disorders