Splicing Machinery Facilitates Post-Transcriptional Regulation by FBFs and Other RNA-Binding Proteins in Caenorhabditis elegans Germline.
Genetic interaction screens are an important approach for understanding complex regulatory networks governing development. We used a genetic interaction screen to identify cofactors of FBF-1 and FBF-2, RNA-binding proteins that regulate germline stem cell proliferation in Caenorhabditis elegans. We found that components of splicing machinery contribute to FBF activity as splicing factor knockdowns enhance sterility of fbf-1 and fbf-2 single mutants. This sterility phenocopied multiple aspects of loss of fbf function, suggesting that splicing factors contribute to stem cell maintenance. However, previous reports indicate that splicing factors instead promote the opposite cell fate, namely, differentiation. We explain this discrepancy by proposing that splicing factors facilitate overall RNA regulation in the germline. Indeed, we find that loss of splicing factors produces synthetic phenotypes with a mutation in another RNA regulator, FOG-1, but not with a mutation in a gene unrelated to posttranscriptional regulation (dhc-1). We conclude that inefficient pre-mRNA splicing may interfere with multiple posttranscriptional regulatory events, which has to be considered when interpreting results of genetic interaction screens.
Division of Biological Sciences, University of Montana, Missoula, Montana 59812.
Preston
P
Novak
Division of Biological Sciences, University of Montana, Missoula, Montana 59812.
Xiaobo
X
Wang
Division of Biological Sciences, University of Montana, Missoula, Montana 59812.
Mary
M
Ellenbecker
Division of Biological Sciences, University of Montana, Missoula, Montana 59812.
Sara
S
Feilzer
Division of Biological Sciences, University of Montana, Missoula, Montana 59812 ekaterina.voronina@umontana.edu.
Ekaterina
http://orcid.org/0000-0002-0194-4260
E
Voronina
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D005804:Genes, Lethal; D005854:Germ Cells / Q000378:metabolism; D009154:Mutation; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional; D012326:RNA Splicing; D016601:RNA-Binding Proteins / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D016601:RNA-Binding Proteins
RNA-binding protein; germline; splicing factor; stem cells