In vivo effects on intron retention and exon skipping by the U2AF large subunit and SF1/BBP in the nematode Caenorhabditis elegans

The in vivo analysis of the roles of splicing factors in regulating alternative splicing in animals remains a challenge. Using a microarray-based screen, we identified a Caenorhabditis elegans gene, tos-1, that exhibited three of the four major types of alternative splicing: intron retention, exon skipping, and, in the presence of U2AF large subunit mutations, the use of alternative 3' splice sites. Mutations in the splicing factors U2AF large subunit and SF1/BBP altered the splicing of tos-1. 3' splice sites of the retained intron or before the skipped exon regulate the splicing pattern of tos-1. Our study provides in vivo evidence that intron retention and exon skipping can be regulated largely by the identities of 3' splice sites

A New Class of C. elegans synMuv Genes Implicates a Tip60/NuA4-like HAT Complex as a Negative Regulator of Ras Signaling

AbstractThe class A and class B synMuv genes are functionally redundant negative regulators of a Ras signaling pathway that induces C. elegans vulval development. A number of class B synMuv genes encode components of an Rb and histone deacetylase complex that likely acts to repress transcription of genes required for vulval induction. We discovered a new class of synMuv genes that acts redundantly with both the A and B classes of genes in vulval cell-fate determination. These new class C synMuv genes encode TRRAP, MYST family histone acetyltransferase, and Enhancer of Polycomb homologs, which form a putative C. elegans Tip60/NuA4-like histone acetyltransferase complex. A fourth gene with partial class C synMuv properties encodes a homolog of the mammalian SWI/SNF family ATPase p400. Our findings indicate that the coordinated action of two chromatin-modifying complexes, one with histone deacetylase and the other with histone acetyltransferase activity, is important in regulating Ras signaling and specifying cell fates during C. elegans development

Modulation of caenorhabditis elegans infection sensitivity by the LIN-7 cell junction protein

10.1111/j.1462-5822.2012.01824.xCellular Microbiology14101584-1599CEMI

Three novel mutations and two variants in the gene for Cu/Zn superoxide dismutase in familial amyotrophic lateral sclerosis

Autosomal dominant inheritance is exhibited by about 10% of cases of amyotrophic lateral sclerosis (ALS), a paralytic disorder characterized by death of motor neurons in the brain and spinal cord. A subgroup of these familial cases are linked to mutations in the gene which codes for Cu/Zn superoxide dismutase (SOD1). We report three additional mutations occurring in the SOD1 gene in ALS patients and two single base pair variant changes. The single base pair change in an ALS family causes a glycine 93 to valine substitution, which is the fifth distinct amino acid change reported for the glycine 93 residue. One missense mutation in exon 5 would substitute neutral valine for the negatively-charged aspartate 124 (aspartate 124 to valine). An individual with an apparently sporadic case of ALS carries a three base pair deletion in exon 5 of the SOD1 gene. These three mutations bring to 38 the total number of distinct SOD1 mutations associated with familial ALS

Linkage of familial amyotrophic lateral sclerosis with frontotemporal dementia to chromosome 9q21-q22

Context Occasionally, 2 or more major neurodegenerative diseases arise simultaneously, An understanding of the genetic bases of combined disorders, such as amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD), will likely provide insight into mechanisms of these and related neurodegenerative diseases, Objective To identify loci that contain genes whose defects cause ALS. Design A genome-wide linkage analysis of 2 data sets from an ongoing study begun in the mid-1980s at 4 university research centers, Subjects An initial subset of 16 families (549 people) potentially informative for genetic analysis, in which 2 or more individuals were diagnosed as having ALS, identified from a Boston data set of 400 families and 4 families potentially informative (244 people) subsequently identified from a Chicago data set of more than 300 families to test a hypothesis based on findings from the Boston families, Main Outcome Measures Linkage calculations assuming autosomal dominant inheritance with age-dependent penetrance (a parametric logarithm-of-odds [lod] score of 1.0 or greater required for further study of a potential locus); crossover analysis involving the ALS-FTD locus, Results In a set of families in which persons develop both ALS and FTD or either ALS or FTD alone, a genetic locus that is linked to ALS with FTD located between markers D9S301 and D9S167 was identified on human chromosome 9q21-q22, Families with ALS alone did not show linkage to this locus. Crossover analysis indicates this region covers approximately 77 cM, Conclusion These data suggest that a defective gene located in the chromosome 9q21-q22 region may be linked to ALS with FTD

Apoptosis of pancreatic acinar cells in acute pancreatitis: Is it good or bad?

10.1111/j.1582-4934.2004.tb00330.xJournal of Cellular and Molecular Medicine83402-40