Linked Life Data

12490553

Source:http://linkedlifedata.com/resource/pubmed/id/12490553

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-12-19
pubmed:abstractText
Alternative splicing of the Sex-lethal pre-mRNA has long served as a model example of a regulated splicing event, yet the mechanism by which the female-specific SEX-LETHAL RNA-binding protein prevents inclusion of the translation-terminating male exon is not understood. Thus far, the only general splicing factor for which there is in vivo evidence for a regulatory role in the pathway leading to male-exon skipping is sans-fille (snf), a protein component of the spliceosomal U1 and U2 snRNPs. Its role, however, has remained enigmatic because of questions about whether SNF acts as part of an intact snRNP or a free protein. We provide evidence that SEX-LETHAL interacts with SANS-FILLE in the context of the U1 snRNP, through the characterization of a point mutation that interferes with both assembly into the U1 snRNP and complex formation with SEX-LETHAL. Moreover, we find that SEX-LETHAL associates with other integral U1 snRNP components, and we provide genetic evidence to support the biological relevance of these physical interactions. Similar genetic and biochemical approaches also link SEX-LETHAL with the heterodimeric splicing factor, U2AF. These studies point specifically to a mechanism by which SEX-LETHAL represses splicing by interacting with these key splicing factors at both ends of the regulated male exon. Moreover, because U2AF and the U1 snRNP are only associated transiently with the pre-mRNA during the course of spliceosome assembly, our studies are difficult to reconcile with the current model that proposes that the SEX-LETHAL blocks splicing at the second catalytic step, and instead argue that the SEX-LETHAL protein acts after splice site recognition, but before catalysis begins.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0950-1991
pubmed:author
pubmed:issnType
Print
pubmed:volume
130
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
463-71
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12490553-Alternative Splicing, pubmed-meshheading:12490553-Amino Acid Sequence, pubmed-meshheading:12490553-Animals, pubmed-meshheading:12490553-Animals, Genetically Modified, pubmed-meshheading:12490553-Drosophila Proteins, pubmed-meshheading:12490553-Drosophila melanogaster, pubmed-meshheading:12490553-Exons, pubmed-meshheading:12490553-Female, pubmed-meshheading:12490553-Gene Expression Regulation, Developmental, pubmed-meshheading:12490553-Genes, Insect, pubmed-meshheading:12490553-Homeostasis, pubmed-meshheading:12490553-Male, pubmed-meshheading:12490553-Models, Genetic, pubmed-meshheading:12490553-Molecular Sequence Data, pubmed-meshheading:12490553-Nuclear Proteins, pubmed-meshheading:12490553-Point Mutation, pubmed-meshheading:12490553-RNA Splicing, pubmed-meshheading:12490553-RNA-Binding Proteins, pubmed-meshheading:12490553-Ribonucleoprotein, U1 Small Nuclear, pubmed-meshheading:12490553-Ribonucleoproteins, pubmed-meshheading:12490553-Sequence Homology, Amino Acid, pubmed-meshheading:12490553-Sex Differentiation
pubmed:year
2003
pubmed:articleTitle
Sex-lethal splicing autoregulation in vivo: interactions between SEX-LETHAL, the U1 snRNP and U2AF underlie male exon skipping.
pubmed:affiliation
Department of Genetics, Case Western Reserve University, Cleveland, OH 44106-4955, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.