ben-gurion university research focus on riboswitches bioinformatics research focus: searching for...
TRANSCRIPT
Ben-Gurion University
Research focus on riboswitches Bioinformatics
Research Focus: Searching for Novel Riboswitches in Newly Sequenced Genomes
Danny Barash†
Department of Computer Science
Ben-Gurion University
†email: [email protected]
Biological Application: RNAs
Ben-Gurion University
Research focus on riboswitches Bioinformatics
Why RNAs? Classical Picture:
DNA RNA PROTEINS
Transcription Translation
New Picture: RNA*
DNA PROTEINS
RNA* : RiboNucleic Acid
Ben-Gurion University
Research focus on riboswitches Bioinformatics
“Riboswitches”: RNA genetic control elements that influence transcription termination or translation initiation by conformation rearrangement of the RNA in response to direct metabolite binding.
Since the mid-90’s, Breaker has been trying to artificially design RNA switches that respond to metabolite binding (Soukup and Breaker, Trends. Biotechnol., 1999).
In 2002, both R. Breaker’s lab (Yale) and E. Nudler’s lab (NYU medical school) discovered these RNA genetic control elements in bacteria (Winkler et al., Nature, 2002); (Mironov et al., Cell, 2002).
These RNA regulatory systems are widespreadin bacteria and are speculated to date back toearly times in evolution (perhaps belonging tothe RNA World).
What are Riboswitches?
Ben-Gurion University
Research focus on riboswitches Bioinformatics
Prokaryotic Transcription Termination by Riboswitches
Nudler and coworkers (Mironov et al., Cell, 2002)
TPP-mediatedAttenuation
Control(TPP=thiamin
Pyrophosphate):
Terminator
Anti-terminator
TPP
Ben-Gurion University
Research focus on riboswitches Bioinformatics
With TPP
Vitamin B1 biosynthesis in bacteria:
TPP-mediated attentuation control:
E. Nudler and coworkers:
(Mironov et al., Cell, 2002)
Thiamine pyrophosphate are the metabolites that alter conformation.
What are Riboswitches?
Terminator
Aptamer
Ben-Gurion University
Research focus on riboswitches Bioinformatics
Without TPP
What are Riboswitches?
Anti-terminator
Aptamer
Vitamin B1 biosynthesis in bacteria:
TPP-mediated attentuation control:
E. Nudler and coworkers:
(Mironov et al., Cell, 2002)
Thiamine pyrophosphate are the metabolites that alter conformation.
Ben-Gurion University
Research focus on riboswitches Bioinformatics
Prokaryotic TranslationInitiation by Riboswitches
Breaker and coworkers (Winkler et al., Nature, 2002)
TPP-mediatedAttenuation
Control(TPP=thiamin
Pyrophosphate):
Sequestor
Anti-sequestor
TPP
Ben-Gurion University
Research focus on riboswitches Bioinformatics
Deleterious mutation prediction inTPP riboswitch using RNAMute
(Barash., Nucleic Acids Res., 2003)
Single point mutation
A158U
GCAGAACAATTCAATATGTATTCGTTTAA…
Predict conformationalswitching mutations
RNAMute
Ben-Gurion University
Research focus on riboswitches Bioinformatics
Successful Computer Predictionsof Deleterious Mutations
(Barash and Gabdank, RNA Biology, 2010): special focus review
TPP-mediatedAttenuation
Control(TPP=thiamin
Pyrophosphate):
Terminator
Anti-terminator
TPP
Ben-Gurion University
Research focus on riboswitches Bioinformatics
Searching for riboswitches inSearching for riboswitches ineukaryotes by their aptamereukaryotes by their aptamer
Sequence is not enough, need structure considerations!
Ben-Gurion University
Research focus on riboswitches Bioinformatics
Searching for riboswitches inSearching for riboswitches ineukaryotes by their aptamereukaryotes by their aptamer
(Cohen et al., In Silico Biology, 2008) – a riboswitch in plants?
Our 3-stem junction candidate in plants
Known consensusin bacteria
Ben-Gurion University
Research focus on riboswitches Bioinformatics
III. “Evolution Canyon”: Analyzing Bacillus Subtilis Strains to Examine How Riboswitches Adapt to Extreme Environments.
Riboswitches in Evolution Canyon