1. Cis-Natural Antisense Transcript Fong Koh BMS 265 May 4, 2009

2. YFG Nomenclature PolII Non-overlapping antisense transcript 5’ 3’ Sense RNA 5’3’ Cis-natural antisense transcript 5’ 3’ 5’ 3’ 5’ Cis-NAT PolII Characteristics of cis-NATs: - just like any other mRNA - probably Pol II transcript - spliced, modified, nuclear exported as per normal - Shares sequence complementarity with sense strand partner

3. First Discovery 1972 P RE cICro P RM PRPR

4. First Mechanistic Example E. Coli plasmid ColE1 ori RNA II (preprimer) RNA I (cis-NAT) replication ROM proteins persistent hybrid formation Characteristics of RNA I : - High turnover - Concentration of RNA I proportional to concentration of ColE1 plasmid

5. Other Prokaryotic Modes of Mechanism

6. Eukaryotes cis-NATs Search for cis-NATs using genomic tools

7. Eukaryotic Mechanisms (a) Transcriptional Interference PolII 123 12 31 123 Cis-NAT 12 (b) RNA Masking

8. Sense Gene mRNA cis-NAT 5’ 3’ 5’ 3’ siRNAs RNA editing Inhibition of Gene Expression – + Cis-NAT methylates promoter region (c) dsRNA-dependent mechanisms (d) Antisense-induced methylation

9. 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