Vertebrate small nuclear RNA genes are present in multiple copies. The first example of a bona fide human U6 snRNA gene demonstrated several novel properties. U6 genes are transcribed by RNA polymerase III (pol III), in contrast to the other snRNA genes that are transcribed by RNA polymerase II (pol II). However, vertebrate U6 promoters are highly unusual in that they contain no intragenic control region found in prototypical pol III genes, but are composed of 5' flanking sequence elements found in pol II promoters. The humanU6 promoter is composed of a proximal region, containing a TATA box and a PSE (proximal sequence element, found in all vertebrate snRNA genes), and a distal region, containing an octamer motif and a SPH element.
Here is a model for the human U6-1 gene transcription complex:
Using the UC-Santa Cruz human genome server, we identified eight other loci that potentially encode full-length U6 RNA. Four of these contain promoter elements in their 5'-flanking regions as summarized below:
We have found that these four additional U6 genes are transcribed, albeit at varying levels from the U6-1 gene. Current experiments are focused on further characterization of the full-length human U6 genes, as well as studies on variant U6 genes.