Journal
NUCLEIC ACIDS RESEARCH
Volume 45, Issue 19, Pages 11144-11158Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkx737
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Funding
- Deutsche Forschungsgemeinschaft [DFG-KN498/8-1, DFG-KN489/11-1, DFG-KN498/11-1]
- CellNetworks/EcTop 2
- Alexander von Humboldt Foundation
- Boehringer Ingelheim Fonds PhD Fellowship
- HBIGS Graduate School PhD Fellowship
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Pervasive transcription of genomes generates multiple classes of non-coding RNAs. One of these classes are stable long non-coding RNAs which overlap coding genes in antisense direction (asRNAs). The function of such asRNAs is not fully understood but several cases of antisense-dependent gene expression regulation affecting the overlapping genes have been demonstrated. Using high-throughput yeast genetics and a limited set of four growth conditions we previously reported a regulatory function for similar to 25% of asRNAs, most of which repress the expression of the sense gene. To further explore the roles of asRNAs we tested more conditions and identified 15 conditionally antisense-regulated genes, 6 of which exhibited antisense-dependent enhancement of gene expression. We focused on the sporulation-specific gene SPS100, which becomes upregulated upon entry into starvation or sporulation as a function of the antisense transcript SUT169. We demonstrate that the antisense effect is mediated by its 3 ' intergenic region (3 '-IGR) and that this regulation can be transferred to other genes. Genetic analysis revealed that SUT169 functions by changing the relative expression of SPS100 mRNA isoforms from a short and unstable transcript to a long and stable species. These results suggest a novel mechanism of antisense-dependent gene regulation via mRNA isoform switching.
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