Abstract:
:In an earlier report two P-transposon insertion alleles of the noncoding hsromega gene, hsromega(05241) and P292 were shown to enhance neurodegeneration caused by expression of ataxin-1 protein with expanded poly-Q in a Drosophila model. In present study, we examined the possible relation between hsromega gene expression and toxicity due to poly-Q pathogenesis. The Drosophila hsromega gene produces several noncoding transcripts in almost all cell types, of which the >10 kb long hsromega-n transcript organizes heterogeneous RNA binding (hnRNPs) and related proteins as nucleoplasmic omega speckles. We show that P insertion alleles of the hsromega gene, which cause its overexpression, dominantly enhance neurodegeneration in fly eyes expressing either expanded poly-Q (127Q) or mutant huntingtin protein. Null allele of Hrb87F gene, encoding hnRNPA1, and a novel gene's mutant allele (l(3)pl10(R)), which affects the omega speckles, also dominantly enhance 127Q-induced neurodegeneration. The hsromega-n transcripts or the hnRNPs do not colocalize with the poly-Q nuclear inclusion bodies, neither in hsromega wild type, nor in hsromega mutant background. However, the levels of poly-Q and Hsp70 were significantly higher in hsromega mutant eye discs. Sequestration of hnRNPs and other related RNA-binding proteins by overexpression of hsromega transcripts in hsromega(05241) or in l(3)pl10(R) background or the reduced levels of Hrb87F protein seem to affect nuclear RNA metabolism, thus enhancing the toxicity due to poly-Q expansion.
journal_name
RNA Bioljournal_title
RNA biologyauthors
Sengupta S,Lakhotia SCdoi
10.4161/rna.3.1.2559subject
Has Abstractpub_date
2006-01-01 00:00:00pages
28-35issue
1eissn
1547-6286issn
1555-8584pii
2559journal_volume
3pub_type
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