True genes for human U1 small nuclear RNA. Copy number, polymorphism, and methylation.

The nucleotide sequence of a human U1 small nuclear RNA gene (HU1-1) is presented, along with several hundred nucleotides of its 5' and 3' flanking regions. We demonstrate that the immediate 5' flanking region sequences are a highly specific hydridization probe capable of distinguishing U1 RNA true genes from pseudogenes. The copy number of U1 RNA genes was determined to be constant, about 30/haploid genome equivalent in six different individuals. Nevertheless, several restriction enzyme cleavage site polymorphisms exist in these genes. We also show that C-C-G-G sequences in the vicinity of U1 RNA true genes are not methylated, but they are methylated near pseudogenes. Genomic DNAs of mouse, frog, chicken, and fruit fly contain sequences homologous to the human U1 RNA gene coding region but not to the 5' flanking region. This suggests that sequences important for expression of U1 RNA genes constitute only a minor part of the 5' flanking regions. In the HU1-1 locus, sequences similar to the consensus T-A-T-A-A-A box are located about 45 and 210 base pairs upstream of the point corresponding to the 5' end of the mature RNA. Several additional direct repeats which may be regulatory elements are present in the upstream region. A few short inverted repeats which probably constitute a transcription termination signal are in the region corresponding to the 3' end of the U1 RNA.