論文 - 詳細
| RRC ID | 33221 |
|---|---|
| 著者 | Karres JS, Hilgers V, Carrera I, Treisman J, Cohen SM. |
| タイトル | The conserved microRNA miR-8 tunes atrophin levels to prevent neurodegeneration in Drosophila. |
| ジャーナル | Cell |
| Abstract |
microRNAs (miRNAs) bind to specific messenger RNA targets to posttranscriptionally modulate their expression. Understanding the regulatory relationships between miRNAs and targets remains a major challenge. Many miRNAs reduce expression of their targets to inconsequential levels. It has also been proposed that miRNAs might adjust target expression to an optimal level. Here we analyze the consequences of mutating the conserved miRNA miR-8 in Drosophila. We identify atrophin as a direct target of miR-8. miR-8 mutant phenotypes are attributable to elevated atrophin activity, resulting in elevated apoptosis in the brain and in behavioral defects. Reduction of atrophin levels in miR-8-expressing cells to below the level generated by miR-8 regulation is detrimental, providing evidence for a "tuning target" relationship between them. Drosophila atrophin is related to the atrophin family of mammalian transcriptional regulators, implicated in the neurodegenerative disorder DRPLA. The regulatory relationship between miR-8 and atrophin orthologs is conserved in mammals. |
| 巻・号 | 131(1) |
| ページ | 136-45 |
| 公開日 | 2007-10-5 |
| DOI | 10.1016/j.cell.2007.09.020 |
| PII | S0092-8674(07)01208-1 |
| PMID | 17923093 |
| MeSH | Animals Apoptosis / physiology Base Sequence Behavior, Animal / physiology Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster* / anatomy & histology Drosophila melanogaster* / physiology Gene Expression Regulation* Genes, Reporter MicroRNAs / genetics MicroRNAs / metabolism* Molecular Sequence Data Mutation Nerve Degeneration / metabolism* Oligonucleotide Array Sequence Analysis Phenotype Transcription Factors / genetics Transcription Factors / metabolism* |
| IF | 38.637 |
| 引用数 | 193 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| リソース情報 | |
| ショウジョウバエ | |