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The identities of sym-2, sym-3 and sym-4, three genes that are synthetically lethal with mec-8 in Caenorhabditis
John Yochem1, Leslie R Bell, Robert K Herman
1Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, Minnesota 55455, USA. jyochem@cbs.umn.edu
Abstract:
On the basis of synthetic lethality, five genes in Caenorhabditis elegans are known to be redundant with the mec-8 gene, which encodes a protein that contains two copies of an RNA recognition motif (RRM) and affects alternative RNA splicing. The molecular identities of two of the redundant genes, sym-1 and sym-5, were previously reported. The remaining three genes have now been cloned, and their synthetically lethal phenotypes with mec-8 are described in more detail. Animals homozygous for mec-8 and sym-2 loss-of-function mutations die during late embryogenesis. The SYM-2 predicted protein contains three RRMs; we propose that SYM-2 and MEC-8 can substitute for each other in promoting the maturation of the transcripts of a vital gene. Animals homozygous for mutations in mec-8 and in either sym-3 or sym-4 have the same striking defect: they arrest development just prior to or just after hatching with a pharynx that appears fully formed but is not properly attached to the body cuticle. sym-3 encodes a protein of unknown function with orthologs in Drosophila and mammals. sym-4 encodes a WD-repeat protein and may also have orthologs in Drosophila and mammals. We propose that SYM-3 and SYM-4 contribute to a common developmental pathway that is redundant with a MEC-8-dependent pathway.
Insights
Researchers identified three new genes in Caenorhabditis elegans that are essential for development when combined with mec-8 mutations. These genes, sym-2, sym-3, and sym-4, are redundant with mec-8, highlighting crucial RNA splicing pathways.
Area of Science:
- Genetics
- Developmental Biology
- Molecular Biology
Background:
- The mec-8 gene in Caenorhabditis elegans encodes a protein with RNA recognition motifs (RRMs) crucial for alternative RNA splicing.
- Synthetic lethality studies have identified five genes redundant with mec-8, with sym-1 and sym-5 previously characterized.
Purpose of the Study:
- To identify and characterize the remaining three genes synthetically lethal with mec-8.
- To elucidate the roles of SYM-2, SYM-3, and SYM-4 in development and their relationship with MEC-8.
Main Methods:
- Gene cloning and characterization of loss-of-function mutations.
- Analysis of synthetic lethal phenotypes in Caenorhabditis elegans.
Main Results:
- mec-8 and sym-2 loss-of-function mutations result in embryonic lethality, suggesting functional redundancy in transcript maturation.
- mec-8 and sym-3 or sym-4 mutations cause developmental arrest with pharyngeal defects, indicating roles in a redundant developmental pathway.
- SYM-2 contains three RRMs, while SYM-3 and SYM-4 encode proteins of unknown function and a WD-repeat protein, respectively, with potential orthologs in other species.
Conclusions:
- SYM-2 is functionally redundant with MEC-8, likely substituting in the maturation of vital gene transcripts.
- SYM-3 and SYM-4 participate in a developmental pathway that is redundant with the MEC-8-dependent pathway.
- The identification of these genes provides insights into conserved RNA splicing and developmental mechanisms.
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