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Convergent Transcription at the Ataxin‐7 Locus Produces dsRNA Fragments that are Processed by Dicer‐1
Author(s) -
Ladd Paula D.,
Ward Jaqueline M.,
Lomas Nicole S.,
Pineda Victor V.,
La Spada Albert R.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.747.4
Subject(s) - dicer , biology , transcription (linguistics) , microbiology and biotechnology , exon , spinocerebellar ataxia , gene , antisense rna , trinucleotide repeat expansion , rna , genetics , rna silencing , gene knockdown , locus (genetics) , rna interference , allele , linguistics , philosophy
Spinocerebellar ataxia type 7 is a polyglutamine repeat disease characterized by retinal and cerebellar degeneration. The causative mutation is an expansion of a CAG repeat in the first coding exon of the ataxin‐7 gene. As with other unstable trinucleotide repeat loci, bidirectional transcription occurs at the repeat region, with the antisense transcript overlapping the first and second coding exons of the sense transcript. Interestingly, the antisense transcript is processed into multiple fragments. The 5’‐end of the antisense transcript is retained in the nucleus, while the remaining fragment is exported to the cytoplasm, where it is further processed. RNase A/T1 dsRNA duplex assays indicated the presence of dsRNAs, while northern blot analysis revealed small RNAs (20–60 nt), suggesting small processed RNA fragments are produced by convergent transcription at the ataxin‐7 locus. Dicer‐1 knockdown on primary mouse cerebellar astroctyes with an integrated ataxin‐7 genomic fragment, detected a significant increase in ataxin‐7 sense expression, suggesting evidence for Dicer‐1‐dependent processing. Funding from the NIH supported this research: R01 GM59356 and ARRA award GM59356‐09‐S1.