Lo splicing dellRNA definizione importanza predizione Ing Francesco Piva Gruppo di biologia computazionale e molecolare Dipartimento di Biochimica, Biologia.
Post on 27-Mar-2015
223 Views
Preview:
Transcript
Lo splicing dell’RNA• definizione• importanza• predizione
Ing Francesco PivaGruppo di biologia computazionale e molecolareDipartimento di Biochimica, Biologia e Genetica
Università Politecnica delle MarcheEdificio Scienze 3, Brecce Bianche, Ancona
f.piva@univpm.it
These are synonymous words, are we sure ?
. . . Ala Val Arg . . .
GCA C G T
GTA C G T
CGA C G TAGA G
GCAGTACGAGCAGTACGCGCAGTACGGGCAGTACGTGCAGTAAGAGCAGTAAGGGCAGTCCGAGCAGTCCGCGCAGTCCGGGCAGTCCGTGCAGTCAGAGCAGTCAGGGCAGTGCGAGCAGTGCGCGCAGTGCGGGCAGTGCGTGCAGTGAGAGCAGTGAGGGCAGTTCGAGCAGTTCGCGCAGTTCGGGCAGTTCGTGCAGTTAGAGCAGTTAGG
GCCGTACGAGCCGTACGCGCCGTACGGGCCGTACGTGCCGTAAGAGCCGTAAGGGCCGTCCGAGCCGTCCGCGCCGTCCGGGCCGTCCGTGCCGTCAGAGCCGTCAGGGCCGTGCGAGCCGTGCGCGCCGTGCGGGCCGTGCGTGCCGTGAGAGCCGTGAGGGCCGTTCGAGCCGTTCGCGCCGTTCGGGCCGTTCGTGCCGTTAGAGCCGTTAGG
GCGGTACGAGCGGTACGCGCGGTACGGGCGGTACGTGCGGTAAGAGCGGTAAGGGCGGTCCGAGCGGTCCGCGCGGTCCGGGCGGTCCGTGCGGTCAGAGCGGTCAGGGCGGTGCGAGCGGTGCGCGCGGTGCGGGCGGTGCGTGCGGTGAGAGCGGTGAGGGCGGTTCGAGCGGTTCGCGCGGTTCGGGCGGTTCGTGCGGTTAGAGCGGTTAGG
GCTGTACGAGCTGTACGCGCTGTACGGGCTGTACGTGCTGTAAGAGCTGTAAGGGCTGTCCGAGCTGTCCGCGCTGTCCGGGCTGTCCGTGCTGTCAGAGCTGTCAGGGCTGTGCGAGCTGTGCGCGCTGTGCGGGCTGTGCGTGCTGTGAGAGCTGTGAGGGCTGTTCGAGCTGTTCGCGCTGTTCGGGCTGTTCGTGCTGTTAGAGCTGTTAGG
4 * 4 * 6 = 96Three AAs specified by 96 synonymous words
ATGTAAACGTATATCGTGACAGTGGTCTGTTAGTATTCCTTTAGTCATGGTTT
ATGTAAACTGGTCTGTTATCATGGTTT
Genomic DNA
mRNA
attggaaaccgaaacccgttggtcacctctgcaatagccctccctccctcacttctacaattttgtgacagtggtcttgttttctgcattctctgcttcacgtgcttgttttgttggagcgcgtttgcatgctgctttaaattctgaaatattaaaaaaatttcgaagtttttcagcacatgggatgggagttttgaatttcaattttttaaaaacatttttctgtgattagtgccgtcgtggcacggctgttagccgcctatccggtttattcgatactttGTGAGTTTTTTGTAACTTTATGGTCGTCGAAATGGGAAAACTTGGCCACCAATATAAGTTTGGAAAACAATTTCCTAAAAATAAAATAATTGAACTTTTCCGATGAATAAAAAAATCGATCAGATATTCTGGAAAAAAAATCGATAAATTAATCGATTTTCTTGGAAAATACATCGAAAAATTGAGAAAAATAGAAAAATGAATGTTTTTCGATTACCGATTTATTGATTTTTCGTGAAAACTGAGTTCAGATAATTTTAAAAGCAATGTTTTTCATTTTTCAAATCAGAATCACTATAGTTTTGAAAAATCAATAATTAATTTATTGATTTTTCAATATAATTTTTTGGAAAAAATAGAAAAATCCCTTTCTAAAAGTTTTAAATTTCCAAGAAAAATTCATTTTCAAAATCACCAACGCGCTCTATAGAGTAGTCGATGAAAATCTCCGTTAAGGGTGCATGGGCAAAACGCGCTCGAACGACAATTGTTATTGTATGTTTGGTCTTGCAACGAAAAGTTTGAAAAATTGAAAAAAAGTTGTGTCTGATACATTTTTTTTTGGCATTTTCTGCTATTTTACACCAGAAAAAATTTAATAAACATAAAAAATCGAAATTTTTCAAGTTGGACAATTTTCAGtgagcatcttatccatcctagttctcagttcaggacttgtgcacattcgtttagagccagatattcgcaaagccttttcaccggatgattcagatgctggataGTAAGTGACTACTGACCTTGAAGCCTCCTTCCTCCACCAGTCAGAAATAACACGTTTTTTCGCAATGTTTTTCTTTTTCTAATTCGATTTCCCTTTCTCCCTTTCTTATTGTGATTTGGTCAATGTTTGGTTGACTGGGAAGAAAATTGAATTTTTTTGGAATTCCACTTGAAGTTAAAAAACCCAAAATAAATATTTGATCAAAAATAAATAAGAAAAAAAAGAAAACTTTAAAGCAAATGAAAATTTCGTTCGTAACTATTTTGTTAATTTTTTTAAAACTCCTATTTTAAATATATGCTTTTTGCGGAAATTTCTATAAATTTTTTTACATTTTTCAGtgaaacccgtgtctggctggaatactacggactcgacatctatccggaacgagcattctgtatttttaccgccaagcgcgaaaattccagtattctccaggaaggcgcactggcagacGTAAGTTGATTCTCCGTCACGCCCACTTTTCTGGCGGGAATTTAAAAAATTTCAGatttatactgtggacaatcgactatcggcggcagttggctaccaagatggggatggacgaaaaaattgcgatccactctgcgacttgaacagcccctttcacttgttagcgGTAGGTGGTGGTCTAGGGTGTCATTTTTCGATTTTTTCAATTATTCGATGTTTTTAGTGAAAATCGAAAAATCTAAAAATTGAAAATCGAAAAATGAAAGAAACATTGTTTTTTGGGGACCAAACATCTTAATGAATTTAACAACAGGGAAAACTGAACAGAAACCTGGACGGTCTTATCCCATTTATCTATATTCTTAAAATGAATGATGGAGAAAAAAGTTAAAATAAAAACATTATCAGCTTTTTGTAAGTTTTTCTCAAAAATTGTTCGATTTTTCGATTTTCTAAAAAGTCGAAAAACCGAAACCCTTGGTGGTGGTGGTGGTGGACTAGAAAACTCTTCAACGACCACATGGCAATTTTCAGaatttgacgcggagaaacaatggtaccacaagtgtattcacctatccggatatgccatatagcggactggatattttcctgggacttcacttgagtaatgcggattttggtaagattttttttgaaatgttaaatgaaaagttgaaaaatagtttttatgatttagccactttccagttaaaatttcatttttttaactataaaaagttctggaaaaatg
Struttura tipica dei geni umani
esoni introni
esone1 introne1 esone2 introne2 esone3
esone1
esone1
introne1
esone2
esone2
introne2
esone3
esone3
SPLICING
eliminazione introni
unione esoni
GT GTAG AG
Lo splicing avviene in tutto il trascritto, anche nelle zone non codificanti
R = G, AY = T, C
R C ORI
O
HO RII+
=
R C ORII
O
HO RI+
Meccanismo di splicingestere alcool
due legami fosfoesterici
U2AF
U2AF
U2AFU2AF
arly
U2AF si lega al tratto pirimidinico a valle del sito di ramificazione
snRNP U2 si lega al sito di ramificazione (richiesta idrolisi ATP)
Arg-Ser
le prot SR connettono U2Af con snRNP U1
si legano insieme
snRNP U5 si lega al 5’ss, snRNP U6 si lega a snRNP U2
snRNP U1 è rilasciato, snRNP U5 si sposta dall’esone all’introne, snRNP U6 si lega al 5’ss
snRNP U4 è rilasciato (richiesta idrolisi ATP), snRNP U6 e U2 catalizzano la
transesterificazione, snRNP U5 si lega al 3’ss, il 5’ ss è tagliato e si forma il
cappio
il 3’ss è tagliato e gli esoni vengono saldati insieme, il cappio verrà deramificato
introne (5’ss)
Sm protein
snRNP U1
C5
G16
RBD: RNA binding domain
si appaia al sito di ramificazione
Sm protein
snRNP U2
si appaiano con snRNA U6
U5
U17
3 541 2
1 2 3 5Muscolo cardiaco
1 43 5Muscolo uterino
Lo splicing è tessuto specifico
Esempio di alternative splicing di un gene umano
Alternative splicing tessuto specifico
Tutti i modi di fare splicing alternativo
Alcuni genomi virali subiscono splicing all’interno della cellula ospite
equine infectious anemia virus (EIAV)
AIM:
SPLICING PREDICTION TOOL
pre mRNAsequence
mRNAstructure
attggaaaccgaaacccgttggtcacctctgcaatagccctccctccctcacttctacaattttgtgacagtggtcttgttttctgcattctctgcttcacgtgcttgttttgttggagcgcgtttgcatgctgctttaaattctgaaatattaaaaaaatttcgaagtttttcagcacatgggatgggagttttgaatttcaattttttaaaaacatttttctgtgattagtgccgtcgtggcacggctgttagccgcctatccggtttattcgatactttGTGAGTTTTTTGTAACTTTATGGTCGTCGAAATGGGAAAACTTGGCCACCAATATAAGTTTGGAAAACAATTTCCTAAAAATAAAATAATTGAACTTTTCCGATGAATAAAAAAATCGATCAGATATTCTGGAAAAAAAATCGATAAATTAATCGATTTTCTTGGAAAATACATCGAAAAATTGAGAAAAATAGAAAAATGAATGTTTTTCGATTACCGATTTATTGATTTTTCGTGAAAACTGAGTTCAGATAATTTTAAAAGCAATGTTTTTCATTTTTCAAATCAGAATCACTATAGTTTTGAAAAATCAATAATTAATTTATTGATTTTTCAATATAATTTTTTGGAAAAAATAGAAAAATCCCTTTCTAAAAGTTTTAAATTTCCAAGAAAAATTCATTTTCAAAATCACCAACGCGCTCTATAGAGTAGTCGATGAAAATCTCCGTTAAGGGTGCATGGGCAAAACGCGCTCGAACGACAATTGTTATTGTATGTTTGGTCTTGCAACGAAAAGTTTGAAAAATTGAAAAAAAGTTGTGTCTGATACATTTTTTTTTGGCATTTTCTGCTATTTTACACCAGAAAAAATTTAATAAACATAAAAAATCGAAATTTTTCAAGTTGGACAATTTTCAGtgagcatcttatccatcctagttctcagttcaggacttgtgcacattcgtttagagccagatattcgcaaagccttttcaccggatgattcagatgctggataGTAAGTGACTACTGACCTTGAAGCCTCCTTCCTCCACCAGTCAGAAATAACACGTTTTTTCGCAATGTTTTTCTTTTTCTAATTCGATTTCCCTTTCTCCCTTTCTTATTGTGATTTGGTCAATGTTTGGTTGACTGGGAAGAAAATTGAATTTTTTTGGAATTCCACTTGAAGTTAAAAAACCCAAAATAAATATTTGATCAAAAATAAATAAGAAAAAAAAGAAAACTTTAAAGCAAATGAAAATTTCGTTCGTAACTATTTTGTTAATTTTTTTAAAACTCCTATTTTAAATATATGCTTTTTGCGGAAATTTCTATAAATTTTTTTACATTTTTCAGtgaaacccgtgtctggctggaatactacggactcgacatctatccggaacgagcattctgtatttttaccgccaagcgcgaaaattccagtattctccaggaaggcgcactggcagacGTAAGTTGATTCTCCGTCACGCCCACTTTTCTGGCGGGAATTTAAAAAATTTCAGatttatactgtggacaatcgactatcggcggcagttggctaccaagatggggatggacgaaaaaattgcgatccactctgcgacttgaacagcccctttcacttgttagcgGTAGGTGGTGGTCTAGGGTGTCATTTTTCGATTTTTTCAATTATTCGATGTTTTTAGTGAAAATCGAAAAATCTAAAAATTGAAAATCGAAAAATGAAAGAAACATTGTTTTTTGGGGACCAAACATCTTAATGAATTTAACAACAGGGAAAACTGAACAGAAACCTGGACGGTCTTATCCCATTTATCTATATTCTTAAAATGAATGATGGAGAAAAAAGTTAAAATAAAAACATTATCAGCTTTTTGTAAGTTTTTCTCAAAAATTGTTCGATTTTTCGATTTTCTAAAAAGTCGAAAAACCGAAACCCTTGGTGGTGGTGGTGGTGGACTAGAAAACTCTTCAACGACCACATGGCAATTTTCAGaatttgacgcggagaaacaatggtaccacaagtgtattcacctatccggatatgccatatagcggactggatattttcctgggacttcacttgagtaatgcggattttggtaagattttttttgaaatgttaaatgaaaagttgaaaaatagtttttatgatttagccactttccagttaaaatttcatttttttaactataaaaagttctggaaaaatg
aatttctAGgccgccgatcctaaaAGTgcaccatttcgcAGaAGTacGTacAGTttcccatctatccctAGTgGTcttGTtttctgcattctctgcttcacGTgcttGTtttGTtggAGcgcGTttgcatgctgctttaaattctgaaatattaaaaaaatttcgaAGTttttcAGcacatgggatgggAGTtttgaatttcaattttttaaaaacatttttctGTgattAGTgccGTcGTggcacggctGTtAGccgcctatccgGTttattcgatactttGTGAGTTTTTTGTAACTTTATGGTCGTCGAAATGGGAAAACTTGGCCACCAATATAAGTTTGGAAAACAATTTCCTAAAAATAAAATAATTGAACTTTTCCGATGAATAAAAAAATCGATCAGATATTCTGGAAAAAAAATCGATAAATTAATCGATTTTCTTGGAAAATACATCGAAAAATTGAGAAAAATAGAAAAATGAATGTTTTTCGATTACCGATTTATTGATTTTTCGTGAAAACTGAGTTCAGATAATTTTAAAAGCAATGTTTTTCATTTTTCAAATCAGAATCACTATAGTTTTGAAAAATCAATAATTAATTTATTGATTTTTCAATATAATTTTTTGGAAAAAATAGAAAAATCCCTTTCTAAAAGTTTTAAATTTCCAAGAAAAATTCATTTTCAAAATCACCAACGCGCTCTATAGAGTAGTCGATGAAAATCTCCGTTAAGGGTGCATGGGCAAAACGCGCTCGAACGACAATTGTTATTGTATGTTTGGTCTTGCAACGAAAAGTTTGAAAAATTGAAAAAAAGTTGTGTCTGATACATTTTTTTTTGGCATTTTCTGCTATTTTACACCAGAAAAAATTTAATAAACATAAAAAATCGAAATTTTTCAAGTTGGACAATTTTCAGtgAGcatcttatccatcctAGTtctcAGTtcAGgacttGTgcacattcGTttAGAGccAGatattcgcaaAGccttttcaccggatgattcAGatgctggatAGTAAGTGACTACTGACCTTGAAGCCTCCTTCCTCCACCAGTCAGAAATAACACGTTTTTTCGCAATGTTTTTCTTTTTCTAATTCGATTTCCCTTTCTCCCTTTCTTATTGTGATTTGGTCAATGTTTGGTTGACTGGGAAGAAAATTGAATTTTTTTGGAATTCCACTTGAAGTTAAAAAACCCAAAATAAATATTTGATCAAAAATAAATAAGAAAAAAAAGAAAACTTTAAAGCAAATGAAAATTTCGTTCGTAACTATTTTGTTAATTTTTTTAAAACTCCTATTTTAAATATATGCTTTTTGCGGAAATTTCTATAAATTTTTTTACATTTTTCAGTgaaacccGTGTctggctggaatactacggactcgacatctatccggaacgAGcattctGTatttttaccgccaAGcgcgaaaattccAGTattctccAGgaAGgcgcactggcAGacGTAAGTTGATTCTCCGTCACGCCCACTTTTCTGGCGGGAATTTAAAAAATTTCAGatttatactGTggacaatcgactatcggcggcAGTtggctaccaAGatggggatggacgaaaaaattgcgatccactctgcgacttgaacAGcccctttcacttGTtAGcgGTAGGTGGTGGTCTAGGGTGTCATTTTTCGATTTTTTCAATTATTCGATGTTTTTAGTGAAAATCGAAAAATCTAAAAATTGAAAATCGAAAAATGAAAGAAACATTGTTTTTTGGGGACCAAACATCTTAATGAATTTAACAACAGGGAAAACTGAACAGAAACCTGGACGGTCTTATCCCATTTATCTATATTCTTAAAATGAATGATGGAGAAAAAAGTTAAAATAAAAACATTATCAGCTTTTTGTAAGTTTTTCTCAAAAATTGTTCGATTTTTCGATTTTCTAAAAAGTCGAAAAACCGAAACCCTTGGTGGTGGTGGTGGTGGACTAGAAAACTCTTCAACGACCACATGGCAATTTTCAGaatttgacgcggAGaaacaatgGTaccacaAGTGTattcacctatccggatatgccatatAGcggactggatattttcctgggacttcacttgAGTaatgcggattttgGTaAGattttttttgaaatGTtaaatgaaaAGTtgaaaaatAGTttttatgatttAGccactttccAGTtaaaatttcatttttttaactataaaaAGTtctggaaaaatG
Segnali per il riconoscimento degli introni
Motivi conservati
I segnali dei siti di splicing sono ben conservati tra le specieprobabilmente la comparsa del meccanismo di splicing è molto antica
5’splice sites
Binding of DAZAP1 and hnRNPA1/A2 to an Exonic Splicing Silencer in a Natural BRCA1 Exon 18 MutantGoina E, Skoko N, Pagani F. Mol Cell Biol 2008; 28: 3850–3860
One point mutation at a time
BRCA1 exon 18
17 18 19
17 19
20%
80%17 18 19
100%
Two point mutations at a time
BRCA1 exon 18
Binding of DAZAP1 and hnRNPA1/A2 to an Exonic Splicing Silencer in a Natural BRCA1 Exon 18 MutantGoina E, Skoko N, Pagani F. Mol Cell Biol 2008; 28: 3850–3860
Complete exon 18 skipping Decreased efficiency
WT 5’-ACAGTTGTTGGCGGTTG-3’TACCACCC TTATTGGTTC AA CCGC G G T
0102030405060708090
100
G T G A G T C T C G C A C A C A C C T T C A G T T C T
WT 144A145C 146A 147G 148T 149T150G 151T 153G 154G 155C 156G 157G
ex9 +ex9 -
% e
xon
9 in
clu
sion
Effect of variations in CFTR exon 9
Pagani, F., Buratti, E., Stuani, C., and Baralle, F. E. (2003) J Biol Chem Pagani, F., Stuani, C., Zuccato, E., Kornblihtt, A. R., and Baralle, F. E. (2003) J Biol Chem
A
pathological
path
olog
ical
path
olog
ical
An additional exonic constraints: the splicing code
The genetic code is degenerate, but it is not all rodustness
. . . Ala Val Arg . . .
GCA C G T
GTA C G T
CGA C G TAGA G
GCAGTACGAGCAGTACGCGCAGTACGGGCAGTACGTGCAGTAAGAGCAGTAAGGGCAGTCCGAGCAGTCCGCGCAGTCCGGGCAGTCCGTGCAGTCAGAGCAGTCAGGGCAGTGCGAGCAGTGCGCGCAGTGCGGGCAGTGCGTGCAGTGAGAGCAGTGAGGGCAGTTCGAGCAGTTCGCGCAGTTCGGGCAGTTCGTGCAGTTAGAGCAGTTAGG
GCCGTACGAGCCGTACGCGCCGTACGGGCCGTACGTGCCGTAAGAGCCGTAAGGGCCGTCCGAGCCGTCCGCGCCGTCCGGGCCGTCCGTGCCGTCAGAGCCGTCAGGGCCGTGCGAGCCGTGCGCGCCGTGCGGGCCGTGCGTGCCGTGAGAGCCGTGAGGGCCGTTCGAGCCGTTCGCGCCGTTCGGGCCGTTCGTGCCGTTAGAGCCGTTAGG
GCGGTACGAGCGGTACGCGCGGTACGGGCGGTACGTGCGGTAAGAGCGGTAAGGGCGGTCCGAGCGGTCCGCGCGGTCCGGGCGGTCCGTGCGGTCAGAGCGGTCAGGGCGGTGCGAGCGGTGCGCGCGGTGCGGGCGGTGCGTGCGGTGAGAGCGGTGAGGGCGGTTCGAGCGGTTCGCGCGGTTCGGGCGGTTCGTGCGGTTAGAGCGGTTAGG
GCTGTACGAGCTGTACGCGCTGTACGGGCTGTACGTGCTGTAAGAGCTGTAAGGGCTGTCCGAGCTGTCCGCGCTGTCCGGGCTGTCCGTGCTGTCAGAGCTGTCAGGGCTGTGCGAGCTGTGCGCGCTGTGCGGGCTGTGCGTGCTGTGAGAGCTGTGAGGGCTGTTCGAGCTGTTCGCGCTGTTCGGGCTGTTCGTGCTGTTAGAGCTGTTAGG
4 * 4 * 6 = 96Three AAs specified by 96 synonymous words
exon31cryptic exonNF1 gene
A>G
ttttatagTGAGAATA
WT MUT
Raponi M, Upadhyaya M, Baralle D.Functional splicing assay shows a pathogenic intronic mutation in neurofibromatosis type 1 (NF1) due to intronic sequence exonization.Hum Mutat. 2006; 27(3):294-295.
La mutazione attiva un esone criptico (in rosso)
TAGgtaataTAGgtggga
TAGataataCAGgtattg
CAAgtattgCAAgtaagc
CAAgtaagg
Raponi M, Upadhyaya M, Baralle D.Functional splicing assay shows a pathogenic intronic mutation in neurofibromatosis type 1 (NF1) due to intronic sequence exonization.Hum Mutat. 2006;27(3):294-295.
exon31cryptic exonNF1 gene
Disruption of 5’ss restores normal splicing
La seq 2 ha un sito di splicing in 5’ più debole della seq 1. La seq 3 non ha il sito.
ATM gene structure
20 21
M WT del mut
20 21
20 21
mutations
results
A new type of mutation causes a splicing defect in ATMPagani F, Buratti E, Stuani C, Bendix R, Dörk T, Baralle FENature Genetics 2002, 30: 426-429
20 21
WT: GGCCAGGTAAGTGATA
DEL: GGCCAG____GTGATA
MUT: GGCCAGGTCTGTGATA
exonic splicing enhancer ESE
exonic splicing silencer ESS
intronic splicing enhancer ISE
intronic splicing silencer ISS
Many elements regulate the splicing process
A compact formalism, but…
scorematrix
Experimental assessed binding sites
ACG
TGconsensus
sequence
AGGAGTCGGCGT
unzip
AGGAGTCGTAGGCGT
Compression and reconstruction of motifs
zip
Intron definition / exon definition
Modello di exonic splicing enhancer mediato da proteine SR
Modello di exonic splicing silencer
elements promoting exons
elements promoting introns
ESE, ISS: esone
ESS, ISE: introne
9G8, CUG-BP1, DAZAP1, ETR-3, Fox-1, Fox-2, FMRP, hnRNP A0, hnRNP A1, hnRNP A2/B1, hnRNP C, hnRNP C1, hnRNP C2, hnRNP D, hnRNP D0, hnRNP DL, hnRNP E1, hnRNP E2, hnRNP F, hnRNP G, hnRNP H1, hnRNP H2, hnRNP I (PTB), hnRNP J, hnRNP K, hnRNP L, hnRNP LL, hnRNP M, hnRNP P (TLS), hnRNP Q, hnRNP U, HTra2alpha, HTra2beta1, HuB, HuD, HuR, KSRP, MBNL1, Nova-1, Nova-2, nPTB, PSF, RBM4, RBM25, Sam68, SAP155, SC35, SF1, SF2/ASF, SLM-1, SLM-2, SRp20, SRp30c, SRp38, SRp40, SRp54, SRp55, SRp75, TDP43, TIA-1, TIAL1, YB-1, ZRANB2 …
PROTEINS REGULATING SPLICING STORED IN SPLICEAID
SEQUENCESPLICEAID COMPETING TOOLS
EXPERIMENTALLY ASSESSED BINDING ESE Finder Rescue ESE Splicing
Rainbow ACAAC YB-1 no binding no ESE SRp40
GAAGAAGAHTra2A, HTra2B1, SF2/ASF, SC35, SRp40, SRp55, SRp75
no binding 3 ESE Tra2B
CUGGCGUCGUCGC no binding SF2/ASF, SRp55 2 ESE SRp40, SRp55
UGACUG hnRNP A1 no binding no ESE SRp40, SRp55
UUUUAGACAA
hnRNP C1, Sam68, hnRNP A1, hnRNP D, hnRNP E1, hnRNP E2, SRp38
no binding 1 ESE
hnRNP A2/B1, hnRNP C1/C2, hnRNP E1/E2, SRp40, SRp55, U2AF65
UGUGUGUGUGUGUGUGUG CUG-BP1, ETR-3, TDP43 SRp55 no ESE hnRNP U
Some comparisons among literature data (SpliceAid) and prediction tools
Pan troglodytesaverage nucleotide divergence of just 1.2%
Suggested papers
Nature reviews. Genetics. 2002; 3(4): 285-298Listening to silence and understanding nonsense: exonic mutations that affect splicing.Cartegni L, Chew SL, Krainer AR.PMID: 11967553
Nature reviews. Genetics. 2007; 8(10): 749-761. Splicing in disease: disruption of the splicing code and the decoding machinery.Wang GS, Cooper TA.PMID: 17726481
top related