High impact information on snf

• SNF/SWI homologs have now been identified in Drosophila, mice and humans, suggesting a conserved role in transcriptional activation [1].
• In sharp contrast to its essential role in U2 snRNP recruitment in vitro, the RS domain on the Drosophila large subunit homolog (dU2AF50) was completely dispensable in vivo [2].
• U2AF binds the intron pyrimidine tract between the branchpoint and the 3' splice site and recruits U2 snRNP to the branch site at an early step in spliceosome assembly [2].
• Previous studies have suggested that snf plays a role in regulating Sex-lethal splicing [3].
• We have cloned snf and found that it has sequence homology to the mammalian U1A and U2B" snRNP proteins [3].

Biological context of snf

• Finally, with the isolation and analysis of a null mutation, we demonstrate that snf is an essential gene [3].
• The gene splicing-necessary factor (snf), which encodes a component of U1 and U2 snRNPs, participates in this RNA splicing control [4].
• 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 [5].
• We show that the previously described yeast open reading frame YIB9w encodes yeast U2B' as judged by the fact that the protein encoded by YIB9w bindsto stem-loop IV of yeast U2 snRNA in vitro and is part of the U2 snRNP in vivo [6].
• Moreover, we find snf is required for normal cell growth and/or survival, as expected for a protein involved in a cell-vital process such as RNA splicing [7].

Anatomical context of snf

• Here we show that an increase in the dose of snf+ can trigger the female Sxl RNA splicing mode in male germ cells and can feminize triploid intersex (2X3A) germ cells [4].
• U2AF binds site specifically to the intron pyrimidine tract between the branchpoint and the 3' splice site and targets U2 snRNP to the branch site at an early step in spliceosome assembly [8].
• Recent findings suggest that functional diversification among SWI/SNF complexes allows the eukaryotic cell to fine-tune and integrate the execution of diverse biological programs involving the expression, maintenance and duplication of its genome [9].

Associations of snf with chemical compounds

• Independently of pre-mRNA, SRm160/300 specifically interacts with U2 snRNP and with a human homolog of the Drosophila alternative splicing regulator Transformer 2, which binds to purine-rich ESEs [10].
• The prevalence of serine amino acids at all specificity determining positions suggests that ARIDs within SWI/SNF-related complexes will interact with DNA non-sequence specifically [11].
• Functional Differentiation of SWI/SNF Remodelers in Transcription and Cell Cycle Control [12].

Physical interactions of snf

• Here we show that Drosophila U2A' protein interacts with SNF in vivo and, like its human counterpart, is U2 snRNP specific [13].
• U2 auxiliary factor (U2AF) is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site [14].

Other interactions of snf

• Its role, however, has remained enigmatic because of questions about whether SNF acts as part of an intact snRNP or a free protein [5].
• Females double heterozygous for fl(2)d and snf1621 are fully viable and fertile. fl(2)d2 in heterozygosis partially suppresses the phenotype of female germ cells homozygous for snf1621; however, this is not the case with the fl(2)d1 mutation [15].
• Unexpectedly, however, we find that loss of function causes lethality, suggesting that U2A', but not SNF, is critical for U2 snRNP function [13].
• Sex determination in Drosophila: the X-chromosomal gene liz is required for Sxl activity [16].
• Multiple developmental requirements of noisette, the Drosophila homolog of the U2 snRNP-associated polypeptide SP3a60 [17].

Analytical, diagnostic and therapeutic context of snf

• The Xenopus BRG1-like protein elutes at a Mr of approximately 2 000 000 on Superose HR6trade mark size-exclusion chromatography, indicating that it is part of a larger complex, as are all other known SWI/SNF proteins [18].

References