Reference Report

Reference
Citation	Houseley, J.M., Wang, Z., Brock, G.J., Soloway, J., Artero, R., Perez-Alonso, M., O'Dell, K.M., Monckton, D.G. (2005). Myotonic dystrophy associated expanded CUG repeat muscleblind positive ribonuclear foci are not toxic to Drosophila. Hum. Mol. Genet. 14(6): 873--883. (Export to RIS)
FlyBase ID	FBrf0184024
Publication Type	Research paper
PubMed ID	15703191
PubMed Abstract	Myotonic dystrophy type 1 is an autosomal dominant disorder associated with the expansion of a CTG repeat in the 3' untranslated region (UTR) of the DMPK gene. Recent data suggest that pathogenesis is predominantly mediated by a gain of function of the mutant transcript. In patients, these expanded CUG repeat-containing transcripts are sequestered into ribonuclear foci that also contain the muscleblind-like proteins. To provide further insights into muscleblind function and the pathogenesis of myotonic dystrophy, we generated Drosophila incorporating CTG repeats in the 3'-UTR of a reporter gene. As in patients, expanded CUG repeats form discrete ribonuclear foci in Drosophila muscle cells that co-localize with muscleblind. Unexpectedly, however, foci are not observed in all cell types and muscleblind is neither necessary nor sufficient for their formation. The foci are dynamic transient structures with short half-lifes that do not co-localize with the proteasome, suggesting they are unlikely to contain mis-folded proteins. However, they do co-localize with non-A, the human orthologs of which are implicated in both RNA splicing and attachment of dsRNA to the nuclear matrix. Muscleblind is also revealed as having a previously unrecognized role in stabilizing CUG transcripts. Most interestingly, Drosophila expressing (CUG)162 repeats has no detectable pathological phenotype suggesting that in contrast to expanded polyglutamine-containing proteins, neither the expanded CUG repeat RNA nor the ribonuclear foci are directly toxic.
DOI
Related Publication(s)
Recent Updates
Description	What does this section display? This section contains items that were added to this record for each release. It currently only tracks new links between this FlyBase report and other FlyBase data classes (e.g. genes, references, stocks) or controlled vocabulary terms (e.g. GO, anatomy terms). What does this section not display? This section does not currently display links that were removed or gene model changes.
Update Feed	Click the icon below to subscribe to this FlyBase record and receive updates automatically through your feed reader.
FB2013_03
FB2013_02
All updates	Click here to see a list of all updates to this record from FB2010_08 and on.
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
Language of Publication	English
Additional Languages of Abstract
Also Published As
Parent Publication
Publication Type	Journal
Abbreviation	Hum. Mol. Genet.
Title	Human Molecular Genetics
Publication Year	1992-
ISBN/ISSN	0964-6906
Data from Reference
Alleles (10)
	Avic\GFP^{Scer\UAS.Hsap\DMPK.CTG11} Avic\GFP^{Scer\UAS.Hsap\DMPK.CTG48} Avic\GFP^{Scer\UAS.Hsap\DMPK.CTG56} Avic\GFP^{Scer\UAS.Hsap\DMPK.CTG162} Hsap\MBNL1^{Scer\UAS.cGCa} mbl^A.Scer\UAS mbl^C.Scer\UAS Scer\GAL4^D42 Scer\GAL4^elav.PU Scer\GAL4^how-24B
Constructs (8)
	P{elav-GAL4.U} P{UAS-GFP.CTG11} P{UAS-GFP.CTG48} P{UAS-GFP.CTG56} P{UAS-GFP.CTG162} P{UAS-KIAA0428} P{UAS-mbl.A} P{UAS-mbl.C}
Genes (8)
	Avic\GFP Hsap\MBNL1 mbl nonA REG Rrp6 Scer\GAL4 Spt6
Insertions (2)
	P{GawB}D42 P{GawB}how^24B
Natural transposons (1)
	P-element