Multiple, dispersed human U6 small nuclear RNA genes with varied transcriptional efficiencies

Abstract

Vertebrate U6 small nuclear RNA (snRNA) gene promoters are among the founding members of those recognized by RNA polymerase III in which all control elements for initiation are located in the 5'-flanking region. Previously, one human U6 gene (U6-1) has been studied extensively. We have identified a total of nine full-length U6 loci in the human genome. Unlike human U1 and U2 snRNA genes, most of the full-length U6 loci are dispersed throughout the genome. Of the nine full-length U6 loci, five are potentially active genes (U6-1, U6-2, U6-7, U6-8 and U6-9) since they are bound by TATA-binding protein and enriched in acetylated histone H4 in cultured human 293 cells. These five all contain OCT, SPH, PSE and TATA elements, although the sequences of these elements are variable. Furthermore, these five genes are transcribed to different extents in vitro or after transient transfection of human 293 cells. Of the nine full-length U6 loci, only U6-7 and U6-8 are closely linked and contain highly conserved 5'-flanking regions. However, due to a modest sequence difference in the proximal sequence elements for U6-7 and U6-8, these genes are transcribed at very different levels in transfected cells.

Evolution of Spliceosomal snRNA Genes in Metazoan Animals

“…[67] counts 16 U1, 6 U2 and 44 U6 snRNAs in the human genome (compared to our 8, 3, and 7, resp. ), while [14] report 5-9 U6 snRNA genes, consistent with our list. Similarly, only a fraction of the major spliceosomal snRNAs reported for the chicken genome in [27] pass our promoter analysis.…”

“…They were manually compared with previously published sequence elements. We visually compared the MEME -patterns with the upstream elements in related species from the following literature sources: [26] (general motifs), [14,82,2,38] (human), [36,5] (chicken), [53] (insects), [77] (Bombyx mori), [81] (Strongylocentrotus purpuratus), [84] (Caenorhabditis elegans).…”

“…The classical snRNA-specific PSE and TATA elements that have been described in detail for several vertebrates [26,14] are highly conserved. This appers to be an exception rather than the rule, however: the snRNA upstream elements are highly diverse across metazoa.…”

“…Distinguishable snRNA paralogs that are often differentially expressed have previously been reported for a diverse collection of major spliceosmal snRNAs including U1 snRNAs in insects [43,64,77], Xenopus [12], and human [39], U2 snRNAs in Dictyostelium [29], sea urchin [80] and silk moth [77], U5 snRNAs in human [79], sea urchin [52], and Drosophilids [8], U6 snRNAs in silk moth [78] and human [85,14].…”

Evolutionary patterns of non-coding RNAs

“…U7 RNA-like sequences are abundant in mammalian genomes, as determined by a blast search of the U7 sequence against the genomic sequence with a cutoff of E = 10 −10 . tebrates and are known to be subject to concerted evolution in some species [84,247,295,431]. Divergent paralogs are also known in some species: For example, Xenopus has distinct embryonic and somatic classes of U1 snRNAs [70].…”