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Mount Bioinformatics
• Chp 8 Prediction of RNA Secondary Structure
• pp. 327-355
• Ck Errata: http://www.bioinformaticsonline.org/help/errata2.html
Promoter Prediction
• Overview of strategies
What sequence signals can be used?
What other types of information can be used?
Fig 5.10
Baxevanis &
Ouellette 2005
10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 10
Promoter prediction strategies
1) Pattern-driven algorithms
2) Sequence-driven algorithms
3) Combined "evidence-based"
Fig 5.14
Baxevanis &
Ouellette 2005
10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 17
Check out optional review &
try associated tutorial:
More lists:
• http://www.softberry.com/berry.phtml?topic=index&group=programs&subgroup=promo
ter
• http://bioinformatics.ubc.ca/resources/links_directory/?subcategory_id=104
• http://www3.oup.co.uk/nar/database/subcat/1/4/
Rob Knight
Univ Colorado
10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 22
Covalent & non-covalent bonds in RNA
Primary:
Covalent bonds
Secondary/Tertiary
Non-covalent bonds
• H-bonds
(base-pairing)
• Base stacking
Fig 6.2
Baxevanis &
Ouellette 2005
10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 23
Base-pairing in RNA
Helices
Loops
• Hairpin
• Interior
• Bulge
• Multibranch
Pseudoknots
Fig 6.2
Baxevanis &
Ouellette 2005
10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 25
RNA functions
• Storage/transfer of genetic information
• Structural
• Catalytic
• Regulatory
• Genomes
• many viruses have RNA genomes
single-stranded (ssRNA)
e.g., retroviruses (HIV)
double-stranded (dsRNA)
Catalytic
RNA in ribosome has peptidyltransferase activity
• Enzymatic activity responsible for peptide
bond formation between amino acids in growing
peptide chain
• Also, many small RNAs are enzymes
"ribozymes" (W Allen Miller, ISU)
C Burge 2005 10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 31
Expression of a Typical Eukaryotic Gene
Protein Coding Gene
…
DNA
Transcription Polyadenylation
exon intron
Protein
Folding, Modification,
Transport, Complex
Assembly
Protein Complex
Degradation
C Burge 2005 10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 32
Gene Expression Challenges for
Computational Biology
Lots of data
Genomes, structures, transcripts, microarrays, ChIP-Chip, etc.
C Burge 2005 10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 33
Steps in Transcription
» Regulatory modules
C Burge 2005 10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 35
Sequence-specific Transcription Factors
C Burge 2005 10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 36
Integration of
transcription &
RNA processing
C Burge 2005 10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 37
Early Steps in Pre-mRNA Splicing
C Burge 2005 10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 38
Alternative Splicing
C Burge 2005 10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 39
Splicing Regulation
C Burge 2005 10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 40
Coupling of Splicing & Nonsense-mediated
mRNA Decay (NMD)
C Burge 2005 10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 41
C. elegans lin-4 Small Regulatory RNA
lin-4 precursor
lin-4 RNA
target mRNA
lin-4 RNA
V. Ambros lab “Translational
repression”
C Burge 2005 10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 42
MicroRNA Biogenesis
C Burge 2005 10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 43
miRNA and RNAi pathways
microRNA pathway RNAi pathway
MicroRNA primary transcript Exogenous dsRNA, transposon, etc.
Drosha
siRNAs
miRNA
target mRNA
RISC
RISC RISC
“translational repression”
and/or mRNA degradation
mRNA cleavage, degradation
C Burge 2005 10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 44
miRNA Challenges for Computational Biology
• Find the genes encoding microRNAs
• Predict their regulatory targets
Computational Prediction of MicroRNA Genes & Targets
C Burge 2005 10/31/05 D Dobbs ISU - BCB 444/544X: RNA Structure & Function 45