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Cis-Natural Antisense Transcript. Fong Koh BMS 265 May 4, 2009. PolII. Sense RNA. 5’. 3’. 3’. 5’. Cis-natural antisense transcript. 3’. 5’. Non-overlapping antisense transcript. Nomenclature. PolII. 5’. 3’. YFG. Cis-NAT. 3’. 5’. Characteristics of cis-NATs:
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Cis-Natural Antisense Transcript Fong Koh BMS 265 May 4, 2009
PolII Sense RNA 5’ 3’ 3’ 5’ Cis-natural antisense transcript 3’ 5’ Non-overlapping antisense transcript Nomenclature PolII 5’ 3’ YFG Cis-NAT 3’ 5’ Characteristics of cis-NATs: - just like any other mRNA - probably PolII transcript - spliced, modified, nuclear exported as per normal - Shares sequence complementarity with sense strand partner
First Discovery PRE PRM PR cI Cro 1972
First Mechanistic Example RNAII (preprimer) E. Coli plasmid ColE1 RNAI (cis-NAT) ROM proteins ori replication persistent hybridformation Characteristics of RNAI: - High turnover- Concentration of RNAI proportional toconcentration of ColE1 plasmid
Eukaryotes cis-NATs Search for cis-NATs using genomic tools
Eukaryotic Mechanisms (a) Transcriptional Interference PolII (b) RNA Masking 1 2 1 2 3 1 3 1 2 3 1 2 Cis-NAT
(c) dsRNA-dependent mechanisms 5’ Sense Gene mRNA 3’ cis-NAT 3’ 5’ RNA editing siRNAs Inhibition of Gene Expression Inhibition of Gene Expression (d) Antisense-induced methylation + – Cis-NAT methylates promoter region
Last words… Cis-Natural Antisense Transcript Unknown > Known Broad category of RNAs Many different functions and mechanisms No evolutionary conservation No significant partner RNA/protein No significant potential for tool No significant role in disease