Genes for human U4 small nuclear RNA

A study of human genes coding for U4 small nuclear RNA is presented. It is known from previous studies that mammalian cells contain three major U4 RNA species, designated U4A, U4B, and U4C (Krol and Branlant, 1981). A clone was isolated from a human DNA library which contained two transcriptionally active genes for U4 RNA. U4 transcription was sensitive to low concentrations of alpha-amanitin, inferring that U4 RNA is a product of RNA polymerase II or RNA polymerase II-like activity. One of the two genes contains a coding region which matches the sequence of U4C RNA perfectly. The coding region of the second gene resembles U4B RNA although there are two differences between the sequence of this gene and the U4B RNA sequence, suggesting that it may encode a minor, hitherto undetected U4 RNA species. The 5'-flanking regions of the two U4 genes contain several almost perfectly conserved sequence motifs. One is located between positions -50 and -60. This motif is present in equivalent positions in the two U4 genes as well as in human U1 and U2 genes. A second motif, which is 19 nucleotides (nt) long and centered around nt position -140, is present in the two U4 genes but absent from U2 RNA genes. A third highly conserved region, located between nt positions -210 and -250, is a putative enhancer element. It includes one copy of the so-called octanucleotide motif, previously identified as adjacent to the early SV40 promoter and immunoglobulin promoters. Another highly conserved sequence motif, CTCTGTGA, is located approximately one helical turn upstream from the octanucleotide motif in both U2 and U4 genes. The human genome appears to contain a family of U4 RNA genes comprising at least 100 copies.