PUBLICATION

RNA-Seq analysis in mutant zebrafish reveals role of U1C protein in alternative splicing regulation

Authors
Rösel, T.D., Hung, L.H., Medenbach, J., Donde, K., Starke, S., Benes, V., Rätsch, G., and Bindereif, A.
ID
ZDB-PUB-110511-10
Date
2011
Source
The EMBO journal   30(10): 1965-1976 (Journal)
Registered Authors
Keywords
znRNP, splicing, zebrafish
MeSH Terms
  • Alternative Splicing*
  • Animals
  • Embryo, Nonmammalian/physiology
  • Gene Expression Regulation*
  • Genetic Complementation Test
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Mutation
  • RNA Precursors/chemistry
  • RNA Precursors/metabolism
  • Ribonucleoproteins, Small Nuclear/genetics
  • Ribonucleoproteins, Small Nuclear/metabolism*
  • Sequence Analysis, DNA
  • Zebrafish/genetics
  • Zebrafish/physiology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
(all 18)
PubMed
21468032 Full text @ EMBO J.
Abstract
Precise 5' splice-site recognition is essential for both constitutive and regulated pre-mRNA splicing. The U1 small nuclear ribonucleoprotein particle (snRNP)-specific protein U1C is involved in this first step of spliceosome assembly and important for stabilizing early splicing complexes. We used an embryonically lethal U1C mutant zebrafish, hi1371, to investigate the potential genomewide role of U1C for splicing regulation. U1C mutant embryos contain overall stable, but U1C-deficient U1 snRNPs. Surprisingly, genomewide RNA-Seq analysis of mutant versus wild-type embryos revealed a large set of specific target genes that changed their alternative splicing patterns in the absence of U1C. Injection of ZfU1C cRNA into mutant embryos and in vivo splicing experiments in HeLa cells after siRNA-mediated U1C knockdown confirmed the U1C dependency and specificity, as well as the functional conservation of the effects observed. In addition, sequence motif analysis of the U1C-dependent 5' splice sites uncovered an association with downstream intronic U-rich elements. In sum, our findings provide evidence for a new role of a general snRNP protein, U1C, as a mediator of alternative splicing regulation.
Genes / Markers
Marker Marker Type Name
abcf1GENEATP-binding cassette, sub-family F (GCN20), member 1
abi2bGENEabl-interactor 2b
aup1GENEAUP1 lipid droplet regulating VLDL assembly factor
bcl7aGENEBAF chromatin remodeling complex subunit BCL7A
brd2aGENEbromodomain containing 2a
btbd10aGENEBTB (POZ) domain containing 10a
btf3GENEbasic transcription factor 3
cbx5GENEchromobox homolog 5 (HP1 alpha homolog, Drosophila)
ccnt2aGENEcyclin T2a
cdkn1bbGENEcyclin dependent kinase inhibitor 1Bb
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Figures
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
snrpchi1371Tg/hi1371Tgstandard conditionsPec-fin
snrpchi1371Tg/hi1371Tgstandard conditionsPec-fin
snrpchi1371Tg/hi1371Tgstandard conditionsPec-fin
snrpchi1371Tg/hi1371Tgstandard conditionsPec-fin
snrpchi1371Tg/hi1371Tgstandard conditionsPec-fin
snrpchi1371Tg/hi1371Tgstandard conditionsPec-fin
snrpchi1371Tg/hi1371Tgstandard conditionsProtruding-mouth
snrpchi1371Tg/hi1371Tgstandard conditionsProtruding-mouth
snrpchi1371Tg/hi1371Tgstandard conditionsProtruding-mouth
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
hi1371TgTransgenic Insertion
1 - 1 of 1
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Human Disease / Model
No data available
Sequence Targeting Reagents
No data available
Fish
Antibodies
No data available
Orthology
Engineered Foreign Genes
No data available
Mapping
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Citation
Rösel, T.D., Hung, L.H., Medenbach, J., Donde, K., Starke, S., Benes, V., Rätsch, G., and Bindereif, A. (2011) RNA-Seq analysis in mutant zebrafish reveals role of U1C protein in alternative splicing regulation. The EMBO journal. 30(10):1965-1976.