Small nuclear RNAs (snRNAs), when complexed with specific proteins, are cofactors in pre-messenger RNA processing and are therefore essential for fundamental pathways of gene expression in eukaryotic cells. Promoters for the most abundant snRNA genes (U1, U2, U4, U5, U6) are some of the most powerful ones in rapidly-growing cells. It has been estimated that a new snRNA transcript that is destined for completion must be initiated every 2 to 4 seconds. Therefore, our study of the snRNA gene transcriptional apparatus will provide insight into the characteristics of highly efficient promoters.
Our work is focused on the human U6-1 snRNA gene promoter (see hU6genes.html). Efficient transcription of this gene is governed by the enhancer-like distal region. The composition of the U6 distal region is very similar to that of other snRNA gene distal regions. Two DNA control elements have been identified in the U6 gene distal region - OCT, bound by Oct-1 transcription activator, and SPH, bound by SBF/Staf transcription activator. We want to understand the mechanism of transcriptional stimulation by the U6 distal region. Current studies are focused on the activation "domain" of SBF/Staf, with the following specific projects: