Coilin-dependent snRNP assembly is essential for zebrafish embryogenesis.
Spliceosomal small nuclear ribonucleoproteins (snRNPs), comprised of small nuclear RNAs (snRNAs) in complex with snRNP-specific proteins, are essential for pre-mRNA splicing. Coilin is not a snRNP protein but concentrates snRNPs and their assembly intermediates in Cajal bodies (CBs). Here we show that depletion of coilin in zebrafish embryos leads to CB dispersal, deficits in snRNP biogenesis and expression of spliced mRNA, as well as reduced cell proliferation followed by developmental arrest. Notably, injection of purified mature human snRNPs restored mRNA expression and viability. snRNAs were necessary but not sufficient for rescue, showing that only assembled snRNPs can bypass the requirement for coilin. Thus, coilin's essential function in embryos is to promote macromolecular assembly of snRNPs, likely by concentrating snRNP components in CBs to overcome rate-limiting assembly steps.
Strzelecka
Magdalena
M
Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany.
Trowitzsch
Simon
S
Weber
Gert
G
Lührmann
Reinhard
R
Oates
Andrew C
AC
Neugebauer
Karla M
KM
D000818:Animals; D049109:Cell Proliferation; D055785:Gene Knockdown Techniques; D005804:Genes, Lethal; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D017411:Ribonucleoproteins, Small Nuclear / Q000378:metabolism / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*
D009687:Nuclear Proteins; D011994:Recombinant Proteins; D017411:Ribonucleoproteins, Small Nuclear; C068921:p80-coilin