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At least 19 recordsLinked to original sources
PubMed1992

Origin of the Alu family: a family of Alu-like monomers gave birth to the left and the right arms of the Alu elements.

The Alu dimeric elements are a common feature of the primate genomes, where they constitute a family of related sequences (1). The identification of a free left Alu monomer (FLAM) family plus a free right Alu monomer (FRAM) family suggests that the dimeric structure results from the fusion of a FLAM sequence with a FRAM sequence (2). Here, we describe a very old Alu-like monomeric family, referred to as FAM for fossil Alu monomer. This family arose from a 7SL RNA sequence and gave birth to the FLAM and FRAM families. From the results obtained, the evolution of the Alu family can be subdivided into two phases. The first phase, which involves only monomeric elements, is characterized by deep remodelling of the progenitor sequences and ends with the appearance of the first Alu dimeric element through the fusion of a FLAM and a FRAM element. The second phase, still in progress, starts with the first Alu dimeric element. This phase is characterized by the stabilization of the progenitor sequences.

Base Sequence↗
PubMed2019

Genome-wide analysis of polymerase III-transcribed Alu elements suggests cell-type-specific enhancer function.

Alu elements are one of the most successful families of transposons in the human genome. A portion of Alu elements is transcribed by RNA Pol III, whereas the remaining ones are part of Pol II transcripts. Because Alu elements are highly repetitive, it has been difficult to identify the Pol III-transcribed elements and quantify their expression levels. In this study, we generated high-resolution, long-genomic-span RAMPAGE data in 155 biosamples all with matching RNA-seq data and built an atlas of 17,249 Pol III-transcribed Alu elements. We further performed an integrative analysis on the ChIP-seq data of 10 histone marks and hundreds of transcription factors, whole-genome bisulfite sequencing data, ChIA-PET data, and functional data in several biosamples, and our results revealed that although the human-specific Alu elements are transcriptionally repressed, the older, expressed Alu elements may be exapted by the human host to function as cell-type-specific enhancers for their nearby protein-coding genes.

Alu Elements↗
PubMed1989

Independent insertion of Alu elements in the human ribosomal spacer and their concerted evolution.

A 2,700-bp segment of human ribosomal DNA (rDNA) spacer upstream of the rRNA promoter contains a set of four Alu elements, two in the direction of rRNA transcription and two in the opposite orientation. We report and compare the sequences of these Alu elements found in three rDNA clones and seek to determine the origin of the cluster, either from a single insertion followed by duplications or from multiple simultaneous or independent insertions. The high (20%-27%) divergence among members of a set and the lack of similarity/complementarity of sequences flanking different members of the set demonstrate the independent insertion of each of the four Alu elements into A-rich sequences on the appropriate strand of the rDNA. We also demonstrate that the Alu sets found in different rDNA repeats are subject to concerted evolution, yielding divergences of only 0.4%-3% between Alu elements in equivalent positions. However, the pairs of adjacent similarly oriented Alu elements do not show reduced divergence, indicating that there is no recombination or gene conversion between similarly oriented but not equivalently positioned Alu elements. Finally, crossing-over must occur in the rDNA junction region between Alu element 3 and the nonribosomal sequences at the telomere end of the acrocentric chromosome, so that the Alu elements of the terminal rDNA repeats and the terminal repeats themselves evolve in concert with the rDNA repeats located internally in the tandem array.

Base Sequence↗
PubMed1992

The RNA polymerase III terminator used by a B1-Alu element can modulate 3' processing of the intermediate RNA product.

The dispersion of short interspersed elements (SINEs) probably occurred through an RNA intermediate. B1 is a murine homolog of the human SINE Alu; these elements are composed of 5' G + C-rich regions juxtaposed to A-rich tracts and are flanked by direct repeats. Internal promoters direct RNA polymerase III to transcribe B1 and Alu elements and proceed into the 3' flanking DNA until it reaches a (dT)4 termination signal. The resulting transcripts contain 3'-terminal oligo(U) tracts which can presumably base pair with the A-rich tract to form self-primed templates for reverse transcriptase and retrotransposition. Nuclear extracts from mouse tissue culture cells contain an RNA processing activity that removes the A-rich and 3'-terminal regions from purified B1 RNAs (R. Maraia, Nucleic Acids Res. 19:5695-5702, 1991). In this study, we examined transcription and RNA processing in these nuclear extracts. In contrast to results with use of purified RNA, nascent transcripts synthesized in nuclear extract by RNA polymerase III are not processed, suggesting that the transposition-intermediate-like RNA is shielded from processing by a protein(s). Alteration of an AATTTT TAA termination signal to a GCTTTTGC signal activated processing by greater than 100-fold in coupled transcription/processing reactions. A similar difference was found when expression was compared in frog oocytes. No difference in processing was found if the transcripts were made by T7 RNA polymerase in the presence of the nuclear extract, indicating that the different processing effects of the two terminators were dependent on synthesis by polymerase III. The modulation of processing of B1-Alu transcripts and the potential for retrotransposition of B1 and Alu DNA sequences are discussed.

Animals↗
PubMed1991

Splice-mediated insertion of an Alu sequence inactivates ornithine delta-aminotransferase: a role for Alu elements in human mutation.

In studies of mutations causing deficiency of ornithine delta-aminotransferase (EC 2.6.1.13), we found an allele whose mature mRNA has a 142-nucleotide insertion at the junction of sequences from exons 3 and 4. The insert derives from an Alu element in ornithine delta-aminotransferase intron 3 oriented in the direction opposite to transcription (an "antisense Alu"). A guanine----cytosine transversion creates a donor splice site in this Alu, activating a cryptic acceptor splice site at its 5' end and causing splice-mediated insertion of an Alu fragment into the mature ornithine-delta-aminotransferase mRNA. We note that the complement of the Alu consensus sequence has at least two cryptic acceptor sites and several potential donor sequences and predict that similar mutations will be found in other genes.

Amino Acid Sequence↗
PubMed1984

Rat prostatic steroid binding protein: characterisation of the Alu element upstream of the C3 genes.

We have characterised an Alu-like repetitive element found about 400 bp upstream of the gene encoding the C3 component of rat prostatic steroid binding protein and suggest, from comparisons with other published sequences, that it is an example of a third class of rodent Alu-equivalent sequences. Members of this class are 80-90 bp long, share greater than 90% sequence homology, and contain sequences resembling the RNA polymerase III bipartite promoter. The Alu type III element within the C3 gene was found to be expressed in cell-free systems and within heterologous cells stably transfected with the C3 gene, but these transcripts were not detectable in rat ventral prostate. It therefore seems unlikely that expression of this sequence plays a role in expression from the adjacent C3 gene.

Androgen-Binding Protein↗
PubMedDate not supplied

[Sequences containing the Alu elements from a human fibroblast cDNA clone library: nucleotide sequence and expression in various tissues].

Alu containing cDNA clones were isolated from a human fibroblast cDNA library. The nucleotide sequences of two clones were determined. In both cases Alu repeats appeared to be situated in the regions presumably corresponding to the 3'-end of mRNA. The comparison of the unique sequences of those clones did not show any homology between them. Both cDNA clones contained large open reading frames, extending into the Alu regions. DNA of one clone was used as a probe for Northern blot-hybridization analysis of poly(A)+ cytoplasmic RNA from some normal and tumor human tissues. All RNA samples contained Alu-homologous transcripts, mainly in 7-12S fractions and only in one (canonical) orientation. This orientation contained functional regions including promotor region for RNA-polymerase III.

Cloning, Molecular↗
PubMed1985

Identification of the short dispersed repetitive DNA sequences isolated from the zones of initiation of DNA synthesis in human cells as Alu-elements.

DNA of Xeroderma pigmentosum cells was crosslinked in vivo with trioxsalen and long wave length ultraviolet light and the cells were cultured in the presence of labelled thymidine for one hour. The nascent DNA chains synthesized during this period and containing the DNA replication origins were isolated from the high molecular weight chromosomal DNA by an alkaline sucrose density gradient centrifugation. They were 5-10-fold enriched in short dispersed repetitive sequences identified by dot-blot hybridization to BLUR 8 plasmid as members of the human Alu-family.

DNA↗
PubMed1991

Complete nucleotide sequence of the gene for human C1 inhibitor with an unusually high density of Alu elements.

The complete (17159 bp) nucleotide sequence of the gene for the human C1 inhibitor has been determined. The transcription initiation site was examined by primer extension using human liver mRNA, and the messenger 5'-end sequence was determined on clones obtained by the anchored polymerase chain reaction. The gene of this serpin molecule is split by seven introns, with junctions of phases zero and one. An outstanding feature of the intron sequences is the occurrence of 17 AluI repeats of all four ancestral subgroups, indicating that the gene has been invaded during consecutive waves of Alu amplification, including a recent one. These Alu repeats form the sites of deletion and insertion in several known lesions in the C1-inhibitor gene. There is no obvious promoter site of the TATA-box type at the 5' end of the gene, but instead it contains a region of potential H-DNA structure similar to that found upstream of the human c-myc gene.

Amino Acid Sequence↗
PubMed1988

Adenosine deaminase (ADA) deficiency due to deletion of the ADA gene promoter and first exon by homologous recombination between two Alu elements.

In 15-20% of children with severe combined immunodeficiency (SCID), the underlying defect is adenosine deaminase (ADA) deficiency. The goal of this study was to determine the precise molecular defect in a patient with ADA-deficient SCID whom we previously have shown to have a total absence of ADA mRNA and a structural alteration of the ADA gene. By detailed Southern analysis, we now have determined that the structural alteration is a deletion of approximately 3.3 kb, which included exon 1 and the promoter region of the ADA gene. DNA sequence analysis demonstrates that the deletion created a novel, complete Alu repeat by homologous recombination between two existing Alu repeats that flanked the deletion. The 26-bp recombination joint in the Alu sequence includes the 10-bp "B" sequence homologous to the RNA polymerase III promoter. This is the first example of homologous recombination involving the B sequence in Alu repeats. Similar recombination events have been identified involving Alu repeats in which the recombination joint was located between the A and B sequences of the polymerase III split promoter. The nonrandom location of these events suggests that these segments may be hot spots for recombination.

Adenosine Deaminase↗
PubMedDate not supplied

Polymorphism near the rat prolactin gene caused by insertion of an Alu-like element.

Primate Alu and rodent Alu-like elements comprise major families of mammalian small dispersed repetitive DNAs. These elements are repeated more than 10(5) times per haploid genome and are found between known genes, in introns and in satellite DNA. Their dispersion throughout the genome and the presence of directly repeated DNA sequences flanking the elements suggest, but do not prove, that they are capable of transposition. We describe here an allelic variation in the 5'-flanking region of the rat prolactin gene that offers the opportunity to examine the sequences of matching regions of two homologous chromosomes which differ in the presence of an Alu-like repetitive DNA element. Our findings support the hypothesis that these elements are integrated into the genome by generating short direct repeats of host DNA.

Alleles↗
PubMed1990

Rapid cloning and characterization of new chromosome 10 DNA markers by Alu element-mediated PCR.

Alu element-mediated polymerase chain reaction is a strategy for rapidly cloning and mapping human DNA markers from mixed DNA sources. A novel primer homologous to the 3' end of the human Alu repeat element provides the basis for preferential synthesis of human DNA fragments from human/rodent somatic cell hybrid DNA template. This approach has been used to isolate a series of new markers from chromosome 10. The Alu element-mediated PCR probes were regionally assigned on chromosome 10 by hybridization to Southern blots of Alu PCR-synthesized DNA derived from somatic cell hybrid template DNA. Alu element-mediated PCR is generally applicable and makes possible the analysis of complex genomes with a speed and sensitivity that has not been previously possible.

Animals↗
PubMed1990

Recombinations between Alu repeat sequences that result in partial deletions within the C1 inhibitor gene.

Genomic DNA sequence analysis was used to define the extent of deletions within the C1 inhibitor gene in two families with type I hereditary angioneurotic edema. Southern blot analysis initially indicated the presence of the partial deletions. One deletion was approximately 2 kb and included exon VII, whereas the other was approximately 8.5 kb and included exons IV-VI. Genomic libraries from an affected member of each family were constructed and clones containing the deletions were analyzed. Sequence analysis of the deletion joints of the mutants and corresponding regions of the normal gene in the two families demonstrated that both deletion joints resulted from recombination of two Alu repetitive DNA elements. Alu repeat sequences from introns VI and VII combined to make a novel Alu in family A, and Alu sequences in introns III and VI were spliced to make a new Alu in family B. The splice sites in the Alu sequences of both mutants were located in the left arm of the Alu element, and both recombination joints overlapped one of the RNA polymerase III promoter sequences. Because the involved Alu sequences, in both instances, were oriented in the same direction, unequal crossingover is the most likely mechanism to account for these mutations.

Angioedema↗
PubMed1986

Amplification of human argininosuccinate synthetase pseudogenes.

The human genome contains multiple pseudogenes for an argininosuccinate synthetase (AS) gene. To elucidate the molecular mechanisms of generation and dispersion, complete nucleotide sequences of four different AS pseudogenes, psi AS-Y, psi AS-A1, psi AS-A2 and psi AS-A3, have been determined. A comparison of these sequences with those of three reported AS pseudogenes, psi AS-1, psi AS-3 and psi AS-7 revealed that two pairs, psi AS-Y/psi AS-7 and psi AS-A3/psi AS-1, are highly homologous but not identical, thereby suggesting that one of the pairs is generated by a duplication of the other member of the pairs. The psi AS-Y, which is probably located on chromosome Y, and the partially sequenced psi AS-7 are both interrupted by an Alu element at exactly the same site in their 3'-end regions. These two Alu elements are located in an opposite orientation relative to the direction of transcription of the pseudogene, and their possible role on pseudogene dispersion was examined. The psi AS-A1 is also accompanied by an Alu element at its 3' end. In this case, the orientation of the Alu element is the same as that of the pseudogene. The psi AS-A1 and the Alu element are flanked with direct repeats, as if they had been inserted into a chromosomal site, as a single unit.

Argininosuccinate Synthase↗
PubMed1991

Serial Alu sequence transposition interrupting a human B creatine kinase pseudogene.

We have isolated, sequenced, and characterized a single-copy B creatine kinase pseudogene. The chromosomal assignment of this gene is 16p13 and a unique sequence probe from this locus detects EcoRI restriction fragment length polymorphisms of 7.8 and 5.4 kb. In 26 unrelated individuals, the frequencies for the 7.8- and 5.4-kb B creatine kinase pseudogene alleles were calculated to be 17.3 and 82.7%, respectively. The B creatine kinase pseudogene is interrupted by a 904-bp DNA insertion composed of three Alu repeat sequences in tandem flanked by an 18-bp direct repeat, derived from the pseudogene sequence. Nucleotide sequence analysis of the Alu elements suggests that the Alu sequences were incorporated into this locus in three separate integration events. Several complex clustered Alu repeat sequences without defined integration borders have been previously identified at different genomic loci. This is the first evidence that complex tandem Alu elements can integrate in an apparently serial manner in the human genome and supports the contention that Alu repeats integrate nonrandomly into the human genome.

Animals↗
PubMed1992

Structure of DNA near long tandem arrays of alpha satellite DNA at the centromere of human chromosome 7.

The centromeric regions of human chromosomes contain long tracts of tandemly repeated DNA, of which the most extensively characterized is alpha satellite. In a screen for additional centromeric DNA sequences, four phage clones were obtained which contain alpha satellite as well as other sequences not usually found associated with tandemly repeated alpha satellite DNA, including L1 repetitive elements, an Alu element, and a novel AT-rich repeated sequence. The alpha satellite DNA contained within these clones does not demonstrate the higher-order repeat structure typical of tandemly repeated alpha satellite. Two of the clones contain inversions; instead of the usual head-to-tail arrangement of alpha satellite monomers, the direction of the monomers changes partway through each clone. The presence of both inversions was confirmed in human genomic DNA by polymerase chain reaction amplification of the inverted regions. One phage clone contains a junction between alpha satellite DNA and a novel low-copy repeated sequence. The junction between the two types of DNA is abrupt and the junction sequence is characterized by the presence of runs of A's and T's, yielding an overall base composition of 65% AT with local areas > 80% AT. The AT-rich sequence is found in multiple copies on chromosome 7 and homologous sequences are found in (peri)centromeric locations on other human chromosomes, including chromosomes 1, 2, and 16. As such, the AT-rich sequence adjacent to alpha satellite DNA provides a tool for the further study of the DNA from this region of the chromosome. The phage clones examined are located within the same 3.3-Mb SstII restriction fragment on chromosome 7 as the two previously described alpha satellite arrays, D7Z1 and D7Z2. These new clones demonstrate that centromeric repetitive DNA, at least on chromosome 7, may be more heterogeneous in composition and organization than had previously been thought.

Animals↗
PubMedDate not supplied

Upstream sequences modulate the internal promoter of the human 7SL RNA gene.

The human genome is rich in sequences which are structurally related to the 7SL RNA component of the signal recognition particle. The 7SL DNA sequence family consists of four 7SL genes, 500 7SL pseudogenes (which are truncated at one or both ends of the 7SL sequence) and 500,000 Alu sequences. Both 7SL genes and Alu elements are transcribed by RNA polymerase III, and we show here that the internal 7SL promoter lies within the Alu-like part of the 7SL gene. Why then does RNA polymerase III transcribe the few 7SL genes so efficiently, while transcripts from the far more abundant Alu elements are not readily detectable? We find that a human 7SL gene and a synthetic Alu sequence derived from it are expressed 50-100-fold more efficiently in vitro than either a representative Alu element or two 7SL pseudogenes. 5' Deletion and insertion mutants of the 7SL gene demonstrate that, in conjunction with the internal promoter, the first 37 nucleotides upstream from the transcription start site are essential for efficient and accurate initiation in vitro. We suggest that the genomic sequences upstream from most Alu elements and 7SL pseudogenes do not contain this element, and consequently that only a small subset of such sequences can be transcribed in vivo. This may help to explain the homogeneity of the Alu family within each mammalian genome, as well as the species-specific differences between mammalian Alu families.

Base Sequence↗