Mutation of RNA Pol III subunit rpc2/polr3b Leads to Deficiency of Subunit Rpc11 and disrupts zebrafish digestive development
- Yee, N.S., Gong, W., Huang, Y., Lorent, K., Dolan, A.C., Maraia, R.J., and Pack, M.
- PLoS Biology 5(11): e312 (Journal)
- Registered Authors
- Yee, Nelson S.
- MeSH Terms
- Cell Proliferation/drug effects
- Digestive System/drug effects
- Digestive System/enzymology
- Digestive System/growth & development*
- Gene Expression Regulation, Developmental*
- Larva/drug effects
- Larva/growth & development
- Oligonucleotides, Antisense/pharmacology
- RNA Polymerase III/genetics*
- RNA Polymerase III/metabolism
- 18044988 Full text @ PLoS Biol.
Yee, N.S., Gong, W., Huang, Y., Lorent, K., Dolan, A.C., Maraia, R.J., and Pack, M. (2007) Mutation of RNA Pol III subunit rpc2/polr3b Leads to Deficiency of Subunit Rpc11 and disrupts zebrafish digestive development. PLoS Biology. 5(11):e312.
The role of RNA polymerase III (Pol III) in developing vertebrates has not been examined. Here, we identify a causative mutation of the second largest Pol III subunit, polr3b, that disrupts digestive organ development in zebrafish slim jim (slj) mutants. The slj mutation is a splice-site substitution that causes deletion of a conserved tract of 41 amino acids in the Polr3b protein. Structural considerations predict that the slj Pol3rb deletion might impair its interaction with Polr3k, the ortholog of an essential yeast Pol III subunit, Rpc11, which promotes RNA cleavage and Pol III recycling. We engineered Schizosaccharomyces pombe to carry an Rpc2 deletion comparable to the slj mutation and found that the Pol III recovered from this rpc2-delta yeast had markedly reduced levels of Rpc11p. Remarkably, overexpression of cDNA encoding the zebrafish rpc11 ortholog, polr3k, rescued the exocrine defects in slj mutants, indicating that the slj phenotype is due to deficiency of Rpc11. These data show that functional interactions between Pol III subunits have been conserved during eukaryotic evolution and support the utility of zebrafish as a model vertebrate for analysis of Pol III function.
Genes / Markers
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes