Human U1 RNA pseudogenes may be generated by both DNA- and RNA-mediated mechanisms.

Abstract

Analysis of cloned human genomic loci homologous to the small nuclear RNA Ut established that such sequences are abundant and dispersed in the human genome and that only a fraction represent bona fide genes. The majority of genomic loci bear defective gene copies, or pseudogenes, which contain scattered base mismatches and in some cases lack the sequence corresponding to the 3' end of Ut RNA. Although all of the Ul genes examined to date are flanked by essentially identical sequences and therefore appear to comprise a single multigene family, we present evidence for the existence of at least three structurally distinct classes of Ul pseudogenes. Class I pseudogenes had considerable flanking sequence homology with the Ut gene family and were probably derived from it by a DNA-mediated event such as gene duplication. In contrast, the Ut sequence in class II and III Ul pseudogenes was flanked by single-copy genomic sequences completely unrelated to those flanking the Ut gene family; in addition, short direct repeats flanked the class III but not the class II pseudogenes. We therefore propose that both class II and III Ut pseudogenes were generated by an RNA-mediated mechanism involving the insertion of Ul sequence information into a new chromosomal locus. We also noted that two other types of repetitive DNA sequences in eucaryotes, the Alu family in vertebrates and the ribosomal DNA insertions in Drosophila, bore a striking structural resemblance to the classes of Ul pseudogenes described here and may have been created by an RNAmediated insertion event.The extensive molecular analysis of eucaryotic genes accomplished in recent years has drastically altered our classical notions of gene structure derived from the study of bacteria. For example, earlier paradigms concerning the strict colinearity between a gene and its product have been undermined by the discovery that intervening sequences interrupt many eucaryotic genes, and the characterization of RNA polymerase III control regions that lie within the transcription unit itself (for a review, see reference 14) has confounded previous ideas about the exclusively upstream location of promoter elements. Similarly, the discovery of extraordinarily varied patterns of gene organization in eucaryotic multigene families and the widespread occurrence in these families of defective gene copies known as pseudogenes (see, for example, references 4, 8, 11, 16, 18, 21, 28, 34, 36, 37, 40, 46, 48, 50, 56) required a major reorientation in our thinking about the structure and evolution of eucaryotic genomes.We have been investigating the structure and organization of the multigene families for the t Present address: Department of Microbiology and Immunology, University of California, San Francisco, CA 94143. human small nuclear RNAs (snRNAs) Ut, U2, and U3. Our previous work established that many or most of the members of each of these families are actually pseudogenes which are dispersed in the human genome (11). DNA sequence analysis of several cloned loci demonstrated that t...

Interruption of an alpha-satellite array by a short member of the KpnI family of interspersed, highly repeated monkey DNA sequences.

“…The similarity between KpnI-RET and pseudogenes includes the polyadenylation signals just upstream from the stretch of A * T base pairs. It has been suggested that these elements may represent a class of movable elements (5,26) distinct from the classical transposable elements (4) and that an RNA intermediate may be involved in the transposition mechanism (7,12,31). That model implies that KpnI-RET may have come from a transcript.…”

The trypanosome spliced leader small RNA gene family: stage-specific modification of one of several similar dispersed genes

“…The most well-studied orphons, aside from those presented here, are those of the histone gene family of the sea urchin (1), those of a gene cluster which encodes six tRNAs in X. laevis (2), and those of the U small nuclear (sn) RNA gene families of man (4,34,35,36 The phylogeny of the orphon flanking regions parallels that of the SL reiteration unit. Despite the fact that trypanosomatids as diverse as L. collosoma, a parasite of insects, and T. brucei, possess sequences homologous to the SL organized in tandem arrays and orphon elements (6), the reiteration unit in which the SL resides is species-specific (40).…”

A U3 RNA pseudogene in mouse: sequence and organization in genomic DNA

“…Instead examination of U3 flanking sequences reveals the classical characteristics of a retroposon sequence [7]: the U3 sequence boundaries correspond precise1.y to the limits of the U3 RNA species; an oligo(A) tail is precisely located at the 3 '-end of the RNA sequence; and the oligo(A) tailed RNA sequence is immediately flanked by a pair of direct repeats at the 5'-and 3 '-ends. By these characteristics, the pklJ- mouse PPlU3 clone clearly belongs to the class III-URNA pseudogenes [9,10]. These pseudogenes are thought to have arisen through an RNAmediated DNA synthesis followed by insertion in the genome, with the flanking repeats likely to result from a repair synthesis at the staggered nicks of the target site.…”

“…Class-III pseudogenes described so far are inserted into sequences present as single copy in the genome [9]. Accordingly the mouse PPl U3 specimen represents a new form of class-III elements.…”