Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Alu elements”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,045 records · Page 58Linked to original sources
PubMed1984

Distinctive sequence organization and functional programming of an Alu repeat promoter.

Plasmid clones containing a human Alu family repeat can be transcribed efficiently by RNA polymerase III in HeLa cell extract. This generated three RNA species, all of which initiated from the first base (+1) of the repeat. By studying the transcriptional properties of deletion clones, subclones, and topologically different DNA templates, we demonstrated that: supercoiled DNA templates are transcribed 3- to 5-fold more efficiently than are linear or nicked circular DNA molecules; a contiguous DNA helix in the transcription complexes that extends into the 5' flanking region of positions -30 to -85 is absolutely required for initiation to occur (this interaction does not involve recognition of specific DNA sequences); and similar to the adenovirus VAI RNA and tRNA genes, the Alu repeat 3' to the alpha 1-globin gene (designated 3'-alpha 1 Alu) contains a split intragenic promoter: an anterior element (positions +4 to +37) and a posterior element (positions +70 to +82). However, the promoter of the Alu repeat functions in distinctive ways in comparison to those of other RNA polymerase III-dependent genes. The posterior promoter element alone is sufficient and necessary for an accurate initiation to occur. The presence of the anterior promoter element, which by itself does not initiate transcription, enhances the transcriptional efficiency by a factor of 10- to 20-fold. Furthermore, the distance between the initiation sites and the posterior promoter element, but not the anterior promoter element, remains constant. These results suggest that the promoter of this Alu family repeat consists of at least two functionally different domains: a "directing element" (the posterior promoter element) that determines the accuracy of initiation and an "enhancing element" (the anterior promoter element) that is mainly responsible for the transcriptional efficiency.

Chromosome Deletion↗
PubMed1994

A master sequence related to a free left Alu monomer (FLAM) at the origin of the B1 family in rodent genomes.

The question of the origin of the B1 family of rodents is addressed. The modern B1 elements are similar to the left Alu monomer, but with a 9 bp deletion and a 29 bp duplication. Search of databases for B1 elements that do not exhibit those modern features revealed sequence fragments that are very similar to the free left Alu monomers (FLAMs) described in the primate genomes. In addition, the analysis reveals elements that have 10 bp or 7 bp deletion in place of the 9 bp deletion but without the 29 bp tandem duplication. The elements described define families of proto B1 elements (referred as PB1, PB1D10 and PB1D7) that appeared before the first modern B1 element. A phylogenetic reconstruction suggest that the origin of Alu and B1 families took place before the divergence between the primate and the rodent lineages and that each family has followed different evolutionary routes since this radiation.

Animals↗
PubMed1993

A cluster of transposon-like repetitive sequences in intron 7 of the human dystrophin gene.

A 32 kilobase-pair fragment of intron 7 of the human dystrophin gene has been sequenced and analysed for the presence of repetitive elements and open reading frames. Two transposon-like human elements (THE-1 sequences), and three intervening, and related, long terminal repeat elements, together with three Alu sequences and a LINE sequence have been identified. These represent an unexpected clustering of highly-repetitive sequences within this single segment of intron DNA. Amplification of a region of chimpanzee genomic DNA by the polymerase chain reaction has provided evidence that at least one of the THE-1 sequences is present in the same position in the chimpanzee genome and the high homology between the human and chimpanzee sequences indicates that this element was fixed within the ancestral genome before the divergence of the two species. The possible role of repetitive, transposon-like sequences in natural mutagenesis of the dystrophin gene is discussed.

Base Sequence↗
PubMed1992

Transcriptional regulation and transpositional selection of active SINE sequences.

Alu repeats are short interspersed elements whose transposition has lead to genetic variability and heritable disorders in humans. A select subset of the nearly one million Alu sequences in human DNA actually produce new transpositions. The evolution of newly inserted Alu repeats is currently a key subject for study. Mechanisms of RNA polymerase III activity and the sequence environment into which an Alu inserts might select for transcriptional and posttranscriptional determinants of Alu transposition.

Animals↗
PubMed2000

Non-homologous recombination between Alu and LINE-1 repeats caused a 430-kb deletion in the dystrophin gene: a novel source of genomic instability.

Although large deletions in the dystrophin gene have been identified in more than two-thirds of Duchenne and Becker muscular dystrophy patients, the molecular mechanisms that lead to the generation of these deletions are largely unknown. Here, Alu and LINE-1 (L1) repetitive elements were shown to be present at one or other of the two ends, respectively, of a 430-kb deletion in the dystrophin gene. The breakpoint of the deletion, which stretches from exons 2 to 7, was defined more precisely by polymerase chain reaction (PCR) walking on introns 1 and 7. Finally, the region containing the breakpoint was amplified as a fragment of more than 10kb. Sequencing of the deletion endpoint revealed the presence of an Alu sequence in intron 1, 25 kb downstream from the 3' end of exon 1 that was joined directly to an L1 sequence in intron 7, 4.5kb downstream from the 3' end of exon 7. The deletion was calculated to be 430kb. To our knowledge, this is a novel recombination event joining non-homologous Alu and L1 repeats, and is the largest known intrachromosomal deletion that is thought to involve repetitive genetic elements. Sequence characteristics around the breakpoint are discussed.

Alu Elements↗
PubMed2026

A single-cell meta-analysis evidences transposable element dysregulation in sex-based differences in Parkinson's disease.

Transposable elements (TEs) (mobile genetic elements comprising ∼45% of the human genome) have recently emerged as potential contributors to Parkinson's disease (PD); however their role and sex-specific impact remain poorly understood. Here, we present the first integrative meta-analysis of TE expression across 4 substantia nigra single-nucleus RNA-seq datasets, comprising a total of 66 donors, generating a cell-type-resolved atlas of TE dysregulation in PD. We identified widespread TE activation across major brain cell types (i.e. neurons, astrocytes, oligodendrocytes and microglia), with marked upregulation of L1s in neurons and HERVs in oligodendrocytes. Sex-stratified analyses revealed distinct male- and female-biased TE signatures, indicating regulatory programs uniquely affected in each sex, including MIR elements in microglia and Alu subfamilies in neurons. Correlation and genomic proximity analyses also uncovered TE-gene associations linked to important PD pathways such as neuroinflammation or myelination. Collectively, our study positions TEs as potential sex-modulated contributors to PD pathology and also provides a public web resource (PATOSS) to explore PD-associated TE transcriptional deregulation.

Parkinson's disease↗
PubMed1996

Expression of novel-transposon-containing mRNAs in human T cells.

The HERV-H family of endogenous retrovirus like elements is the largest such human family known. Using an HERV-H LTR probe, 6 and 4.5 kb transcripts were detected by Northern blot analysis which were induced in normal peripheral T cells after treatment with phytohaemaglutinin (PHA). Expression was not evident 30 min after treatment with phorbol ester, was increased within 3-4 h after treatment, reached a maximum after 8 h and then declined to low levels 24 h after treatment. Expression was inhibited totally by cycloheximide (10 micromolar) and by the immunosuppressant cyclosporin A (1 microgram/ml). Using probes specific for the U3 and U5 regions of the HERV-H LTR, in combination with internal HERV-H probes, evidence was obtained that the 6 and 4.5 kb transcripts are polyadenylated from an HERV-H LTR. A cDNA library was constructed from T cells which had been treated with PHA for 8 h and a 1.7 kb clone was isolated using the HERV-H LTR probe. The insert contained a novel tandem array of an Alu, a LINE-1 element, two endogenous retroviral LTRs and an A-T-rich sequence. The A-T-rich sequence contained multiple copies of AUUUA mRNA regulatory motifs. Because of its high expression level, defined transcription kinetics, novel cassette-like composition and the presence of conserved mRNA stabilization sequences, we hypothesize that the transcript may play a biological role during T cell activation.

Base Sequence↗
PubMed2003

Maple syrup urine disease in the Austronesian aboriginal tribe Paiwan of Taiwan: a novel DBT (E2) gene 4.7 kb founder deletion caused by a nonhomologous recombination between LINE-1 and Alu and the carrier-frequency determination.

Maple syrup urine disease (MSUD) is an autosomal recessive inborn error disorder derived from the accumulation of the branched-chain amino acids (BCAAs) leucine, isoleucine and valine. Either the E1alpha, E1beta or DBT (E2) genes are responsible for this neurometabolic disease. Here, we report the identification and characterization of a novel E2 gene 4.7 kb deletion as a rare nonhomologous recombination of the long interspersed nuclear elements 1 (LINE-1) in intron 10 and the Alu in the 3' UTR of the E2 gene from three classic MSUD patients of the Austronesian aboriginal tribe Paiwan in Taiwan. The E2 gene 4.7 kb deletion accounted for five out of six alleles in the three unrelated Paiwanese MSUD patients, indicating a founder effect. Carrier-frequency study revealed one deleted heterozygote out of 101 normal Paiwanese. As the nine Taiwanese Austronesian aboriginal tribes share a common origin, this E2 4.7 kb deletion may be preserved in some of the other Austronesian aboriginal tribes of Taiwan. This is the first comprehensive genetics study of MSUD in the Austronesian tribal groups as well as in Taiwan.

Alu Elements↗
PubMed2004

i-Genome: a database to summarize oligonucleotide data in genomes.

BACKGROUND: Information on the occurrence of sequence features in genomes is crucial to comparative genomics, evolutionary analysis, the analyses of regulatory sequences and the quantitative evaluation of sequences. Computing the frequencies and the occurrences of a pattern in complete genomes is time-consuming. RESULTS: The proposed database provides information about sequence features generated by exhaustively computing the sequences of the complete genome. The repetitive elements in the eukaryotic genomes, such as LINEs, SINEs, Alu and LTR, are obtained from Repbase. The database supports various complete genomes including human, yeast, worm, and 128 microbial genomes. CONCLUSIONS: This investigation presents and implements an efficiently computational approach to accumulate the occurrences of the oligonucleotides or patterns in complete genomes. A database is established to maintain the information of the sequence features, including the distributions of oligonucleotide, the gene distribution, the distribution of repetitive elements in genomes and the occurrences of the oligonucleotides. The database can provide more effective and efficient way to access the repetitive features in genomes.

Alu Elements↗
PubMed1996

cDNA and genomic cloning of human palmitoyl-protein thioesterase (PPT), the enzyme defective in infantile neuronal ceroid lipofuscinosis.

Palmitoyl-protein thioesterase (PPT) is a small glycoprotein that removes palmitate groups from cysteine residues in lipid-modified proteins. We recently reported mutations in PPT in patients with infantile neuronal ceroid lipofuscinosis (INCL), a severe neurodegenerative disorder (J. Vesa et al., 1995, Nature 376: 584-587). INCL is characterized by the accumulation of proteolipid storage material in brain and other tissues, suggesting that the disease is a consequence of abnormal catabolism of acylated proteins. In the current paper, we report the sequence of the human PPT cDNA and the structure of the human PPT gene. The cDNA predicts a protein of 306 amino acids that contains a 25-amino-acid signal peptide, three N-linked glycosylation sites, and consensus motifs characteristic of thioesterases. Northern analysis of a human tissue blot revealed ubiquitous expression of a single 2.5-kb mRNA, with highest expression in lung, brain, and heart. The human PPT gene spans 25 kb and is composed of seven coding exons and a large eighth exon, containing the entire 3'-untranslated region of 1388 bp. An Alu repeat and promoter elements corresponding to putative binding sites for several general transcription factors were identified in the 1060 nucleotides upstream of the transcription start site. The human PPT cDNA sequence and gene structure will provide the means for the identification of further causative mutations in INCL and facilitate genetic screening in selected high-risk populations.

Amino Acid Sequence↗
PubMed1996

The structure of the prostaglandin EP4 receptor gene and related pseudogenes.

The EP4 prostaglandin receptor (EP4R) is a member of the seven transmembrane receptor superfamily. We have obtained the human EP4 receptor gene sequence and determined its structure relative to EP4R cDNA synthesized from peripheral blood lymphocytes. The EP4R gene spans approximately 22 kb and consists of three exons separated by two introns. The first exon (530 bp) is noncoding. After an intron of 472 bp, the second exon contains a short (43 bp) 5' sequence before a 289-amino-acid open reading frame (ORF). An 11.5-kb intron is found at the end of transmembrane 6, and the rest of the ORF is in exon 3. The gene structure is analogous to those of the thromboxane, PGI, and PGD receptors. The deduced initiation site does not contain a conventional TATA box but is 70% GC-rich and contains CCAAT boxes, SP1 and AP2 motifs, and motifs consistent with activation by proinflammatory cytokines. Southern blot analysis of human genomic DNA shows two genes with homology to the EP4R gene. Both appear to be pseudogenes with 70% amino acid identity to the EP4R up to the "ERY" sequence at the end of transmembrane 3, where an Alu-like repetitive sequence element was found. The ORF sequence is also interrupted by a stop codon. The pseudogenes differ in that one contains a second "repetitive element" (a line 1 repeat) in the 5' end of the ORF. Northern blot analysis of human mRNA using a pseudogene probe showed hybridization only to the EP4 receptor transcript. PCR also failed to detect expression of either pseudogene. This study defines the gene structure of EP4R and suggests the existence of two related pseudogenes.

Amino Acid Sequence↗
PubMed1997

cDNA libraries from single human preimplantation embryos.

In this paper, the construction, evaluation, and application of cDNA libraries from eight unfertilized oocytes and single four-cell-, seven-cell-, and blastocyst-stage embryos are described. Rapid, reproducible, and efficient procedures for the construction of PCR-based cDNA libraries from fewer than 10 cells were first developed in small populations of fibroblast cells. The human embryo libraries display complexities sufficient (between 10(5) and 10(6) clones) to represent the entire active gene population at these early stages of human development. The ubiquitous cytoskeletal elements, beta-actin, keratin-18, and alpha-tubulin, were detected at the expected frequency. Sequencing of consecutively picked random clones, without selection, showed the presence of a variety of sequences, such as the human transposable element, LINE-1 and Alu repeat sequences, housekeeping genes, and tissue-specific genes, such as alpha-globin and FMR-1. In addition to cDNAs corresponding to known ESTs (expressed sequence tags) in the GenBank and dbEST databases, a high proportion of novel sequences were detected. Applications of the libraries to several areas of interest, such as expression of CpG-island-containing "tissue-specific" genes, developmental genes expressed in a stage-specific manner, and a search for monoallelic expression of imprinted genes, are described. The libraries are a valuable resource for the study of gene expression during human preimplantation development and obviate the need for research on the human embryos themselves.

Cells, Cultured↗
PubMed1989

SINEs and LINEs cluster in distinct DNA fragments of Giemsa band size.

By in situ hybridization, short interspersed repeated DNA elements (SINEs), exemplified by Alu repeats, are located principally in Giemsa-light human metaphase chromosome bands. In contrast, the L1 family of long interspersed repeats (LINEs) preferentially cluster in Giemsa-dark bands. These SINE/LINE patterns also generally correspond to early and later replication band patterns. In order to provide a molecular link between structurally visible chromosome bands and a framework of interspersed repeats, we investigated patterns of SINE and LINE hybridization using pulse-field gel electrophoresis (PFGE). Interspersed SINEs and LINEs hybridize with high intensity to specific size fragments of 0.2-3 megabase pairs (Mb). Using appropriate restriction enzymes and pulse-field conditions, a number of fragments were delineated that were either SINE or LINE rich, and were mutually exclusive. Control studies with a human endogenous retroviral repeat that is related in sequence to the major LINE family, delineated a subset of fragments of 0.07-0.4 Mb with unequal intensity. Thus these less numerous repeats also appear to cluster selectively in DNA domains that are larger than a chromosome loop (60-120 kb). In summary, PFGE studies independently confirm the clustering of interspersed repeats on contiguous DNA loops. Selective clustering of repeat motifs may contribute to special structural or functional properties of large chromosome domains, such as chromatin extension/condensation or replication characteristics. In some cases the DNA fragments defined by these repeats approach the size of tandem satellite arrays.

Animals↗
PubMed1992

BC200 RNA in normal human neocortex, non-Alzheimer dementia (NAD), and senile dementia of the Alzheimer type (AD).

BC200 RNA is a polyadenylated 200 nucleotide primate brain-specific transcript with 80% homology to the left monomer of the human Alu family of repetitive elements. Whether this transcription product contributes anything to normal brain gene function or is a residue of post transcriptional processing of brain heterogeneous nuclear RNA (hnRNA) is uncertain. However, the high abundance, tissue-specific expression and nucleotide sequence characteristics of BC200 RNA suggests that the generation of this small RNA is associated with some brain cell function. Sustained levels of the BC200 RNA transcript may be indicative of a genetically competent and normally functioning cerebral neocortex. In this investigation, we have measured the abundance of the BC200 RNA transcript in total RNA isolated from 18 temporal neocortices (Brodman area 22) of brains with no pathology and those affected with neurodegenerative disease. Neocortices were examined from 3 neurologically normal brains, 5 non-Alzheimer demented [NAD; 3 Huntington's chorea (HC), 1 amyotrophic lateral sclerosis (ALS) and 1 dementia unclassified] and 10 Alzheimer disease (AD) affected brains. Our results indicate a strong BC200 presence in both the normal brains and NAD affected neocortices, but a 70 per cent reduction in BC200 signal strength in AD afflicted brains. These results may be related to the observation that Alzheimer brains exhibit marked deficits in the abundance of neuron-specific DNA transcripts; these deficits are consistent with the idea that AD is characterized by an impairment in the primary generation of brain gene transcription products.

Alzheimer Disease↗
PubMed2000

Comparative genomic sequence analysis of the Williams syndrome region (LIMK1-RFC2) of human chromosome 7q11.23.

Williams syndrome (WS) is a complex neurodevelopmental disorder arising from a microdeletion at Chr band 7q11.23, which results in a hemizygous condition for a number of genes. Within this region we have completely characterized 200 kb containing the genes LIMK1, WBSCR1, and RFC2. Evidence was also found for WBSCR5 in this region, but not the previously proposed genes WSCR2 and WSCR6. The syntenic region in mouse was also sequenced (115 kb) and characterized, and a comparative sequence analysis with a percent identity plot (PIP) easily allowed us to identify coding exons. This genomic region is GC rich (50.1% human, 49.9% mouse) and contains an unusually high abundance of repetitive elements consisting primarily of Alu (45.4%, one of the highest levels identified to date) in human, and the B family of SINES (30.6% of the total sequence) in mouse. WBSCR1 corresponds to eukaryotic initiation factor 4H, identified in rabbit, and is herein found to be constitutively expressed in both human and mouse, with two RNA and protein products formed (exon 5 is alternatively spliced). The transcription pattern of WBSCR5 was also examined and discussed along with its putative amino acid sequence.

Amino Acid Sequence↗
PubMed1992

Structure of the rat gene encoding the mitochondrial benzodiazepine receptor.

The gene encoding the rat mitochondrial benzodiazepine receptor (MBR) was cloned and characterized. Hybridization of a previously cloned cDNA for MBR to genomic Southern blots indicated that the gene was probably present at one copy per haploid genome. Rapid amplification of cDNA ends with rat adrenal RNA was used to obtain 47 nt of additional sequence upstream from our previously cloned MBR cDNA proving to be a crucial step in cloning the first exon of this gene. The MBR gene is comprised of four exons spanning approx. 10 kb. The first intron, contained within a 8-kb stretch of this gene, is located within the 5'-untranslated sequence, whereas the remaining two introns are much shorter (641 and 854 bp) and interrupt the coding sequence. The third intron contains sequences homologous to rodent B1 repetitive elements and a novel sequence closely resembling part of a repetitive element belonging to the Alu family in humans. The transcription start point was mapped by S1 nuclease protection assays suggesting that the first exon is just 56 bp in length. The sequence upstream from this region contains three GC boxes but lacks other known consensus recognition sites for sequence-specific transcription factors.

Amino Acid Sequence↗
PubMed1997

Immunohistochemical and genetic evidence of myeloperoxidase involvement in multiple sclerosis.

The myeloperoxidase enzyme (MPO) is expressed specifically in myeloid cells and catalyzes the formation of hypochlorous acid and other cytotoxic oxidants. We previously reported that two alleles of MPO exist which differ in promoter strength due to a base difference in an Alu-encoded hormone response element. The present study shows that the higher expressing MPO genotype is overrepresented in early onset multiple sclerosis in females, implicating MPO in this demyelinating disease. Contrary to the general conception that macrophages lack MPO, immunohistochemical analysis shows that MPO is present in microglia/macrophages in and around MS lesions as shown by colocalization with major histocompatibility antigens HLA-DR and phagocytized myelin. Also, MPO mRNA sequences are detected in cDNA derived from isolated human adult microglia. This is the first evidence that MPO is present in microglia/macrophages at MS lesions, that MPO gene expression occurs in microglia and that MPO plays a role in MS pathogenesis as shown by the allelic disequilibrium in early onset disease.

Adult↗
PubMed1997

Expression of dendritic BC200 RNA, component of a 11.4S ribonucleoprotein particle, is conserved in humans and simians.

Primate BC200 RNA, a brain-specific small cytoplasmic RNA, is one of the few known cell type specific non-messenger RNAs. It originated from a monomeric Alu short interspersed repetitive element (SINE) in primates. In situ hybridization using rhesus monkey (Macaca mulatta) brain sections reveals a similar cellular and sub-cellular distribution as in human brain. In addition to confirming its dendritic location, the distribution in an old world monkey indicates a discrete regional and subcellular location of BC200 RNA. We also report that BC200 RNA exists as a ribonucleoprotein (RNP) particle in vivo. In sucrose gradients, the BC200 particle has a sedimentation constant of about 11.4 S, significantly more than the corresponding 200 nucleotide long naked RNA (approximately 7.6 S).

Animals↗