https://www.cell.com/cell/pdf/0092-8674(82)90414-7.pdf

Self-splicing RNA: Autoexcision and autocyclization of the ribosomal RNA intervening sequence of tetrahymena

https://www.cell.com/cell/pdf/0092-8674(83)90071-5.pdf

Nucleotide sequence of rous sarcoma virus

The processed pseudogenes reported to date fall into three categories: those that are a complete copy of the mRNA transcribed from the functional gene, those that are only a partial copy of the corresponding mRNA, and those that contain sequences in addition to those expected to be present in the mRNA. The general structural characteristics of these processed pseudogenes include the complete lack of intervening sequences found in the functional counterparts, a poly A tract at the 3' end, and direct repeats flanking the pseudogene sequence. In all the cases studied, these pseudogenes have been found to be on a different chromosome from their functional counterpart. These characteristics have led investigators to suggest that an RNA intermediate, in many cases the mRNA of the functional gene, is involved in the production of these pseudogenes. The mechanism by which processed pseudogenes arose involves the integration of the mRNA, or its cDNA copy, into a staggered chromosome break, followed by DNA synthesis and repair. I suggest that all the transcripts that gave rise to these pseudogenes were actually produced in the germ line cell. The transcripts that gave rise to the processed pseudogenes that are direct copies of the corresponding mRNA resulted from RNA polymerase II transcription of the functional counterpart. Pseudogenes that are not a direct copy of the corresponding mRNA may have resulted from RNA polymerase III transcription. If this is indeed the case, one need not postulate the involvement of retroviruses to explain the presence of processed pseudogenes corresponding to genes that are not expressed in the germ line. Following the integration event, processed pseudogenes can no longer be transcribed to produce the functional mRNA from which they arose. This inability to be transcribed by RNA polymerase II is not surprising considering that processed pseudogenes seem to be randomly integrated into the genome. Therefore, integration of a processed pseudogene such that RNA polymerase II transcriptional promoters are correctly positioned 5' to the resultant pseudogene is an unlikely event. The presence of processed pseudogenes seems peculiar to mammals. In fact, evolutionary studies indicate that processed pseudogenes are of relatively recent origin. In fact, at least one processed pseudogene, the human DHFR psi 1, has been formed so recently that it is polymorphic.

Processed Pseudogenes: Characteristics and Evolution

A compensatory base change in U1 snRNA suppresses a 5' splice site mutation

7SL RNA is an abundant cytoplasmic RNA which functions in protein secretion as a component of the signal recognition particle. Alu sequences are the most abundant family of human and rodent middle repetitive DNA sequences (reviewed in ref. 2). The primary structure of human 7SL RNA consists of an Alu sequence interrupted by a 155-base pair (bp) sequence that is unique to 7SL RNA. In order to obtain information about the evolution of the Alu domain of 7SL RNA, we have determined the nucleotide sequence of a cDNA copy of Xenopus laevis 7SL RNA and of the 7SL RNA gene of Drosophila melanogaster. We find that the Xenopus sequence is 87% homologous with its human counterpart and the Drosophila 7SL RNA is 64% homologous to both the human and amphibian molecules. Despite the evolutionary distance between the species, significant blocks of homology to both the Alu and 7SL-specific portions of mammalian 7SL RNA can be found in the insect sequence. These results clearly demonstrate that the Alu sequence in 7SL RNA appeared in evolution before the mammalian radiation. We suggest that mammalian Alu sequences were derived from 7SL RNA (or DNA) by a deletion of the central 7SL-specific sequence, and are therefore processed 7SL RNA genes.

Alu sequences are processed 7SL RNA genes

Direct repeats flank three small nuclear RNA pseudogenes in the human genome

Human U1 Loci: Genes for human U1 RNA have dramatically similar genomic environments

Ul small nuclear RNA (Ul snRNA) is encoded by a large family of genes (30–125 copies/haploid genome) which are transcribed by RNA polymerase II. Ul snRNA is thought to function in gene splicing. Since the Ul genes were found to be >20 kb apart by analyzing genomic phage clones, the chromosomal location of Ul genes in the human genome was determined using Southern filter analysis of DNA isolated from human-rodent somatic cell hybrids and by in situ hybridization. Human DNA digested with PvuII and probed with a Ul-specific probe, pD2, show several major hybridizing fragments. Of these, two human PvuII fragments of 1.4 kb and 2.4 kb had unique mobilities compared to mouse fragments. In a study of 19 cell hybrids, the human-specific Ul fragments segregated with the chromosome 1 markers peptidase C and adenylate kinase 2. All other chromosomes showed>-19% discordancy. An additional 13 karyotyped cell hybrids, analyzed by Southern filter analysis, confirmed the assignment of this class of Ul genes to chromosome 1. Additional digests with MspI and PstI indicated that most Ul genes are located on chromosome 1. To determine if the Ul RNAs are located predominantly at one site or dispersed over chromosome 1, a tritium-labeled Ul probe was hybridized in situ to metaphase chromosomes. The majority of the grains were at band 1p36.3, suggesting that most of the Ul genes are located in this region.

Tim Manser

Papers

Direct repeats flank three small nuclear RNA pseudogenes in the human genome

Human U1 Loci: Genes for human U1 RNA have dramatically similar genomic environments

Localization of Human U1 Small Nuclear RNA Genes to Band p36.3 of Chromosome 1 by In Situ Hybridization

Characterization of small nuclear RNA U1 gene candidates and pseudogenes from the human genome.