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Repeat-Associated Non-AUG Translation of AGAGGG Repeats that Cause X-Linked Dystonia-Parkinsonism
dc.contributor.authorReyes, Charles Jourdan
dc.contributor.authorAsano, Katsura
dc.contributor.authorTodd, Peter K.
dc.contributor.authorKlein, Christine
dc.contributor.authorRakovic, Aleksandar
dc.date.accessioned2022-12-05T16:42:04Z
dc.date.available2023-12-05 11:42:03en
dc.date.available2022-12-05T16:42:04Z
dc.date.issued2022-11
dc.identifier.citationReyes, Charles Jourdan; Asano, Katsura; Todd, Peter K.; Klein, Christine; Rakovic, Aleksandar (2022). "Repeat-Associated Non-AUG Translation of AGAGGG Repeats that Cause X-Linked Dystonia-Parkinsonism." Movement Disorders 37(11): 2284-2289.
dc.identifier.issn0885-3185
dc.identifier.issn1531-8257
dc.identifier.urihttps://hdl.handle.net/2027.42/175246
dc.description.abstractBackgroundX-linked dystonia-parkinsonism (XDP) is a neurodegenerative disorder caused by the intronic insertion of a SINE-VNTR-Alu (SVA) retrotransposon carrying an (AGAGGG)n repeat expansion in the TAF1 gene. The molecular mechanisms by which this mutation causes neurodegeneration remain elusive.ObjectivesWe investigated whether (AGAGGG)n repeats undergo repeat-associated non-AUG (RAN) translation, a pathogenic mechanism common among repeat expansion diseases.MethodsXDP-specific RAN translation reporter plasmids were generated, transfected in HEK293 cells, and putative dipeptide repeat proteins (DPRs) were detected by Western blotting. Immunocytochemistry was performed in COS-7 cells to determine the subcellular localization of one DPR.ResultsWe detected putative DPRs from two reading frames, supporting the translation of poly-(Glu-Gly) and poly-(Arg-Glu) species. XDP RAN translation initiates within the (AGAGGG)n sequence and poly-(Glu-Gly) DPRs formed nuclear inclusions in transfected cells.ConclusionsIn summary, our work provides the first in-vitro proof of principle that the XDP-linked (AGAGGG)n repeat expansions can undergo RAN translation. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
dc.publisherJohn Wiley & Sons, Inc.
dc.subject.otherTAF1
dc.subject.otherSVA retrotransposon
dc.subject.otherrepeat expansion
dc.subject.otherDipeptide repeat proteins
dc.subject.otherRAN translation
dc.subject.otherX-linked dystonia-parkinsonism
dc.titleRepeat-Associated Non-AUG Translation of AGAGGG Repeats that Cause X-Linked Dystonia-Parkinsonism
dc.typeArticle
dc.rights.robotsIndexNoFollow
dc.subject.hlbtoplevelHealth Sciences
dc.description.peerreviewedPeer Reviewed
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/175246/1/mds29183.pdf
dc.description.bitstreamurlhttp://deepblue.lib.umich.edu/bitstream/2027.42/175246/2/mds29183_am.pdf
dc.identifier.doi10.1002/mds.29183
dc.identifier.sourceMovement Disorders
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dc.working.doiNOen
dc.owningcollnameInterdisciplinary and Peer-Reviewed


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