Cis-Natural Antisense Transcript

Fong Koh

BMS 265

May 4, 2009

YFG

Nomenclature

PolII

Non-overlapping antisense transcript

5’3’

Sense RNA5’ 3’

Cis-natural antisense transcript5’3’

5’

3’

3’

5’

Cis-NATPolII

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

1972P

RE

cI Cro

PR

M PR

First Mechanistic Example

E. Coli plasmid ColE1

oriRNAII (preprimer)

RNAI (cis-NAT)

replication

ROM proteins

persistent hybridformationCharacteristics of RNAI:

- High turnover- Concentration of RNAI proportional toconcentration of ColE1 plasmid

Other Prokaryotic Modes of Mechanism

Eukaryotes cis-NATsSearch for cis-NATs using genomic tools

Eukaryotic Mechanisms(a) Transcriptional Interference

PolII

1 2 31 2

31

1 2 3

Cis-NAT

1 2

(b) RNA Masking

Sense Gene mRNA

cis-NAT

5’3’

5’ 3’

siRNAs

RNA editing

Inhibition of Gene Expression Inhibition of Gene Expression

–

+

Cis-NATmethylates

promoter region

(c) dsRNA-dependent mechanisms

(d) Antisense-induced methylation

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