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 1,243 records · Page 69Linked to original sources
PubMed1987

Isolation of three kinds of human endogenous retrovirus-like sequences using tRNA(Pro) as a probe.

Three kinds of human endogenous retrovirus-like sequences (HuERS-P1, 2 and 3) were isolated from a HeLa cell genomic library using the 3'-half fragment of proline tRNA as a hybridization probe. These elements contained putative primer binding sites complementary to the 3'-terminus of proline tRNA and long terminal repeats (LTRs) characteristic of retrovirus provirus. The LTR sequence of HuERS-P1 consisted of about 690 nucleotides and contained a CAT box, a TATA box and a polyadenylation signal. A complete unit of an Alu family sequence was inserted into the 5'-LTR of one of the clones. HuERS-P2 also contained a TATA box and a polyadenylation signal in its LTR (about 840 nucleotides long), but the LTR sequence of this element was quite different from that of HuERS-P1. Although clone HuERS-P3 contained only the 5'-LTR region, this LTR sequence contained a CAT box, a TATA box and a poly-adenylation signal and was quite similar to the LTR sequence of the recently isolated human retrovirus-related sequence HuRRS-P (Kröger, B. and Horak, I. (1987) J. Virol., 61, 2071-2075). Human and simian DNAs contain 10 to 40 copies of these elements, but mouse DNA does not contain these elements.

Base Sequence↗
PubMed1993

Sequential insertion of Alu family repeats into specific genomic sites of higher primates.

The presence of Alu family repeats is closely associated with interspecies length polymorphisms of certain genomic regions among different higher primates. By sequence analysis of cloned DNA, we show that one major cause for the length difference between the gibbon adult alpha-globin locus and those of human, orangutan, and Old World monkeys is the existence of multimeric Alu family repeats. Triplet Alu family repeats exist at two genomic sites of gibbon. Instead, singleton or doublet Alu family repeats are present at the orthologous positions in other higher primates. Sequence comparisons suggest that these doublet and triplet Alu repeats have been created by successive insertion of different singleton Alu repeat sequences, of approximately 300 bp, into the same genomic spot(s) during primate evolution. The approximate dates of insertion of these singleton Alu repeats support the concept of overlapping periods of active transposition or retroposition of Alu repeat subfamilies. This dynamic flow of Alu repeat sequences during primate evolution into the adult alpha-globin loci, but not beta-globin-like loci, is consistent with the previous finding that R-banding regions of the primate chromosomes are enriched in Alu repeats.

Animals↗
PubMed1996

DNA sequence insertion and evolutionary variation in gene regulation.

Current evidence on the long-term evolutionary effect of insertion of sequence elements into gene regions is reviewed, restricted to cases where a sequence derived from a past insertion participates in the regulation of expression of a useful gene. Ten such examples in eukaryotes demonstrate that segments of repetitive DNA or mobile elements have been inserted in the past in gene regions, have been preserved, sometimes modified by selection, and now affect control of transcription of the adjacent gene. Included are only examples in which transcription control was modified by the insert. Several cases in which merely transcription initiation occurred in the insert were set aside. Two of the examples involved the long terminal repeats of mammalian endogenous retroviruses. Another two examples were control of transcription by repeated sequence inserts in sea urchin genomes. There are now six published examples in which Alu sequences were inserted long ago into human gene regions, were modified, and now are central in control/enhancement of transcription. The number of published examples of Alu sequences affecting gene control has grown threefold in the last year and is likely to continue growing. Taken together, all of these examples show that the insertion of sequence elements in the genome has been a significant source of regulatory variation in evolution.

Animals↗
PubMed1982

Long terminal repeat-like elements flank a human immunoglobulin epsilon pseudogene that lacks introns.

There are at least three immunoglobulin epsilon genes (C epsilon 1, C epsilon 2, and C epsilon 3) in the human genome. The nucleotide sequences of the expressed epsilon gene (C epsilon 1) and one (C epsilon 3) of the two epsilon pseudogenes were compared. The results show that the C epsilon 3 gene lacks the three intervening sequences entirely and has a 31-base A-rich sequence 16 bases 3' to the putative poly(A) addition signal, indicating that the C epsilon 3 gene is a processed gene. The C epsilon 3 gene sequence is homologous to the five separate DNA segments of the C epsilon 1 gene; namely, a segment in the 5'-flanking region (100 bases) and four exons, which are interrupted by a spacer region or intervening sequences. Long terminal repeat (LTR)-like sequences which contain TATAAA and AATAAA sequences as well as terminal inverted repeats are present in both 5'- and 3'-flanking regions. The 5' and 3' LTR-like sequences do not, however, constitute a direct repeat, unlike transposable elements of eukaryotes and retroviruses. The 3' LTR-like sequence is repetitive in the human genome, but is not homologous to the Alu family DNA. Models for the evolutionary origin of the processed gene flanked by the LTR-like sequences are discussed. The C epsilon 3 gene has a new open frame which codes potentially for an unknown protein of 292 amino acid residues.

Amino Acid Sequence↗
PubMed1984

Bovine 1.709 satellite. Recombination hotspots and dispersed repeated sequences.

The nucleotide sequence of 3800 base-pair repeated unit of bovine 1.709 satellite was determined. The 3800 base-pair unit is not internally repeated and contains members of at least three different families of elements that are dispersed in the bovine genome. Two of three elements are associated with extensive length polymorphism within the satellite repeat unit. One of these comprises the 3' end of the bovine Alu-like sequences; the second is composed of C-A dinucleotides.

Animals↗
PubMed1984

RNA polymerase III control regions in retrovirus LTR, Alu-type repetitive DNA, and papovavirus.

Sequences analogous to the intragenic bipartite RNA polymerase III promoter regions in tRNA genes, are described in mammalian Alu-type repetitive DNA, LTR of retroviruses and control regions of papovaviruses. The RNA polymerase III control regions in some of these DNA elements are present in enhancer sequences which are known to increase the transcription of RNA polymerase II transcribed genes. It is suggested that the host and tissue specificity of the enhancer elements may be explained by differences in the RNA polymerase III control sequences. The RNA polymerase III promoters may thus participate in regulation of cell differentiation and transcription of tissue specific genes.

Animals↗
PubMed1981

mRNA in human cells contains sequences complementary to the Alu family of repeated DNA.

Approximately one-half of the polysomal poly(A)+RNA from CCRF-CEM human lymphoblastoid cells associates at low R0t (10 M.sec) [where R0 is the initial concentration of RNA (M) and t is time (sec)] to form branched complexes detectable by electron microscopy. The complexes typically involve 2-16 molecules associated over double-stranded regions 120 +/- 30 base pairs long. Formation of such complexes suggests that poly(A)+RNA contains repeated-sequence elements that are highly represented in the mRNA population. Hybridization of polysomal poly(A)+RNA with a recombinant human DNA plasmid, p lambda H15C, which is shown to contain at least three regions complementary to two different members of the Alu family of DNA repeat sequences, showed a total of five regions where R loops are formed. The hybridized regions comprising these groups are 260 +/- 180, 240 +/- 170, 150 +/- 70, 180 +/- 60, and 180 +/- 80 base pairs long. The relative frequencies of R loops formed at these different sites indicate that sequences in this recombinant DNA are represented in the mRNA population at different frequencies. The hybridizing sequence of the RNA molecules is located near one terminus in 13% of the R loops and internally in 53% of the R loops. Surprisingly, 35% of the R loops apparently involve RNA molecules hybridized over their entire length of only 200 +/- 110 base pairs.

Cell Line↗
PubMed1989

Structure and organization of the gene encoding human pulmonary surfactant proteolipid SP-B.

Human pulmonary surfactant proteolipid SP-B arises by proteolytic processing of a 42,000-dalton precursor. The active proteolipid SP-B is one of two small hydrophobic proteins identified in surfactant that impart surface-active properties to surfactant phospholipids. We report the isolation and characterization of complete SP-B cDNA from a human lung cDNA library. The cDNA was used to isolate the gene encoding the SP-B precursor from a lambda EMBL3 library of human embryonic kidney DNA. The entire SP-B gene was sequenced and is approximately 9.5 kb long, with 11 exons and 10 introns including a large 823-nucleotide 3' untranslated exon. The sequence derived from the exons differs from the cDNA sequence at 3 positions out of 2001, only one of which is in the translated region. Direct RNA sequencing indicated that the 5' untranslated region is only 14 nucleotides long. A number of putative regulatory elements were found upstream of the SP-B gene, including a GC box and several putative cAMP and glucocorticoid receptor binding sites. Several Alu repeats and a region of potential Z-DNA formation were found in the introns. Southern blotting of human genomic DNA probed with SP-B cDNA indicated the presence of only one SP-B gene in the human genome, and the gene was localized to chromosome 2.

Amino Acid Sequence↗
PubMed1995

Cell stress and translational inhibitors transiently increase the abundance of mammalian SINE transcripts.

The abundance of Alu RNA is transiently increased by heat shock in human cell lines. This effect is specific to Alu repeats among Pol III transcribed genes, since the abundance of 7SL, 7SK, 5S and U6 RNAs is essentially unaffected by heat shock. The rapid induction of Alu expression precedes the heat shock induction of mRNAs for the ubiquitin and HSP 70 heat shock genes. Heat shock mimetics also transiently induce Alu expression indicating that increased Alu expression is a general cell-stress response. Cycloheximide treatment rapidly and transiently increases the abundance of Alu RNA. Again, compared with other genes transcribed by Pol III, this increase is specific to Alu. However, as distinguished from the cell stress response, cycloheximide does not induce expression of HSP 70 and ubiquitin mRNAs. Puromycin also increases Alu expression, suggesting that this response is generally caused by translational inhibition. The response of mammalian SINEs to cell stress and translational inhibition is not limited to SINEs which are Alu homologues. Heat shock and cycloheximide each transiently induce Pol III directed expression of B1 and B2 RNAs in mouse cells and C-element RNA in rabbit cells. Together, these three species exemplify the known SINE composition of placental mammals, suggesting that mammalian SINEs are similarly regulated and may serve a common function.

3T3 Cells↗
PubMed1992

The human THE-LTR(O) and MstII interspersed repeats are subfamilies of a single widely distributed highly variable repeat family.

Fifteen examples of the transposon-like human element (THE) LTR and thirteen examples of the MstII interspersed repeat are aligned to generate new consensus sequences for these human repetitive elements. The consensus sequences of these elements are very similar, indicating that they compose subfamilies of a single human interspersed repetitive sequence family. Members of this highly polymorphic repeat family have been mapped to at least 11 chromosomes. Seven examples of the THE internal sequence are also aligned to generate a new consensus sequence for this element. Estimates of the abundance of this repetitive sequence family, derived from both hybridization analysis and frequency of occurrence in GenBank, indicate that THE-LTR/MstII sequences are present every 100-3000 kb in human DNA. The widespread occurrence of members of this family makes them useful landmarks, like Alu, L1, and (GT)n repeats, for physical and genetic mapping of human DNA.

Base Sequence↗
PubMed1993

The role of the 5'-flanking region in the cell-specific transcription of the human von Willebrand factor gene.

Transcriptional regulation of the human von Willebrand factor (vWF) gene was investigated in calf pulmonary artery endothelial (CPAE), HeLa, COS 7 and Hep G2 cells. Various lengths of flanking sequences extending up to 2123 bp 5' of the transcription initiation site and containing 19 bp of the first exon, were linked to the bacterial chloramphenicol acetyltransferase (CAT) gene and these constructs were assayed in transient transfection assays. Sequences up to 89 bp upstream of the cap site showed transcriptional activity in all cell types. Sequences between -147 and -419 bp markedly reduced CAT activity in CPAE cells and abolished it in other cell lines. A domain from -592 to -810 bp generated low levels of expression only in CPAE cells. This transcriptional activity was repressed with constructs containing 1041 to 1240 bp upstream of the cap site. Endothelial cell-specific transcription was restored by a construct that contained 1286 bp upstream of the cap site. The additional 46 bp upstream of the negative regulatory domain were within the 5' end of an inverse human Alu-family DNA repeat. RNAase-protection assays confirmed the correct transcriptional initiation. The sequence between -89 and -420 contained at least one negative regulatory element able to repress the CAT gene expression controlled by the heterologous thymidine kinase promoter in all cell types. A construct that included the sequence from -89 to -1286 bp increased the transcriptional activity directed by the thymidine kinase promoter only in CPAE cells. These results indicate that negative and positive elements in the 5'-flanking region interact to regulate vWF gene expression.

Animals↗
PubMed1998

Potential Alu function: regulation of the activity of double-stranded RNA-activated kinase PKR.

Cell stress, viral infection, and translational inhibition increase the abundance of human Alu RNA, suggesting that the level of these transcripts is sensitive to the translational state of the cell. To determine whether Alu RNA functions in translational homeostasis, we investigated its role in the regulation of double-stranded RNA-activated kinase PKR. We found that overexpression of Alu RNA by cotransient transfection increased the expression of a reporter construct, which is consistent with an inhibitory effect on PKR. Alu RNA formed stable, discrete complexes with PKR in vitro, bound PKR in vivo, and antagonized PKR activation both in vitro and in vivo. Alu RNAs produced by either overexpression or exposure of cells to heat shock bound PKR, whereas transiently overexpressed Alu RNA antagonized virus-induced activation of PKR in vivo. Cycloheximide treatment of cells decreased PKR activity, coincident with an increase in Alu RNA. These observations suggest that the increased levels of Alu RNAs caused by cellular exposure to different stresses regulate protein synthesis by antagonizing PKR activation. This provides a functional role for mammalian short interspersed elements, prototypical junk DNA.

Cell Line↗
PubMed1990

Recently transposed Alu repeats result from multiple source genes.

A human Alu repeat subfamily (the PV subfamily) whose members include insertional polymorphisms is found, as predicted, to differ by five tightly linked mutations relative to another subfamily of recently inserted Alu repeats. Based on these sequence differences some of the small number of polymorphic Alus can be selected from the background of nearly one million member sequences which are fixed in the human genome. Shared patterns of mutations suggest that PV subfamily members are the progeny of several different founder sequences. The additional observation that all members of the PV subfamily end in a stretch of uninterrupted polyadenine residues rather than merely A-rich sequences is evidence for post-transcriptional polyadenylation of the presumptive RNA intermediate. The drift of polyadenine sequences toward tandemly repeated A-rich motifs suggests a biological function that may select for the fixation of dispersed Alu repeats.

Base Sequence↗
PubMed1985

Structure and genomic organization of the rat aldolase B gene.

The structure of the chromosomal gene encoding rat aldolase isozyme B has been elucidated by sequence analysis of cloned genomic DNA. This gene comprises about 14 X 10(3) base-pairs of DNA, and is separated into nine exons by eight intervening sequences. A presumed transcription-initiation site was assigned by S1 nuclease protection mapping, and T-A-T-A and C-C-A-A-T boxes were found to be 25 and 126 base-pairs, respectively, upstream from this initiation site. There are three characteristic sequences of 100 to 200 base-pairs within the region of 870 base-pairs flanking the 5' side of the gene. These sequences are flanked on either side by direct repeats and terminate with an A-rich stretch of nucleotides. One of them has block homology with a region in an "ID sequence", which is reported to be an element for tissue-specific gene regulation and differentiation. The other two are analogous at the sequence organizational level with a sort of dispersed repeat, the "Alu family". These features suggest that these regions are involved in gene regulation and, also, imply evolutionary events such as duplication or insertion. Comparison of this gene sequence with the rabbit aldolase A complementary DNA sequence revealed some bias in the frequency of nucleotide replacement among the exons, suggesting selective evolutionary conservation of particular exons encoding functional domains. Comparison with the human aldolase B complementary DNA sequence revealed no such tendency; the homology between the two sequences was very high (about 89%), and nucleotide replacements were randomly distributed throughout the protein-coding region.

Animals↗
PubMed1989

Unique sequence organization and erythroid cell-specific nuclear factor-binding of mammalian theta 1 globin promoters.

The theta 1 globin gene is an alpha globin-like gene, and started to diverge from the other members of the alpha globin family 260 million years ago. DNA sequencing and transcriptional analysis indicated that it is functional in erythroid cells of the higher primates, but not in prosimians and rabbit. The theta 1 promoter region of higher primates including man consists of GC-rich sequences characteristic of housekeeping gene promoters, and CCAAT and TATA boxes located further upstream. It is shown here that the housekeeping gene promoter-like region of human theta 1 contains two tandemly arranged, GC-rich motifs (GC-I and GC-II). Of these, GC-II interacts with nuclear factor(s) present in the globin-expressing, erythroleukemia cell line K562, before and after hemin induction. GC-I, however, interacts with nuclear factor(s) only present in hemin-induced K562 cells. These factors are different from previously reported erythroid cell-specific factors, and are not detectable in non-erythroid Hela cells. Furthermore, the sequence of the motif GC-I and its location relative to ATG codon have been conserved among all known mammalian theta 1 globin genes. Finally, and most interestingly, the CCAAT box of theta 1 is contained within a 38 bp internal segment of Alu repeat sequence. Immediately upstream from this CCAAT box-containing Alu repeat segment is a 241 bp Alu repeat pointing in the opposite direction. The conservation of this novel arrangement among the higher primates suggests that an inserted Alu family repeat and its flanking genomic sequence have co-evolved, for at least 30 million years, to provide the canonical CCAAT and TATA promoter elements of the theta 1 globin genes in higher primates.

Animals↗
PubMed1987

Restriction enzyme evidence for Alu sequence-mediated dispersion of microinjected genes in transgenic mice.

A human bacteriophage clone containing adult beta-globin genes with four Alu sequences was microinjected to produce transgenic mice. Southern blot analysis on the spleen of a transgenic mouse revealed an unusual hybridization pattern that suggested extensive dispersion of human DNA throughout the mouse genome. This pattern was reproducible using several restriction enzymes, including a noncutting enzyme. The hybridization pattern was not observed in other tissues, and sequences were not detected in progeny using the bacteriophage probe. However, hybridization of spleen DNA of offspring against a human Alu probe revealed genetic transmission of human Alu sequences. The results suggest dispersion of microinjected Alu sequences throughout the genome.

Animals↗
PubMed1987

The molecular organization of the H-2K region of two t-haplotypes: implications for the evolution of genetic diversity.

The genetic diversity between the t12 and tw5 haplotype chromosomes was studied by analyzing the molecular organization of the H-2K region. Twenty-one cosmid clones spanning over 150 kb of the H-2K region of both t-haplotypes were defined, and high resolution restriction maps were determined. Detailed comparison of the t12 and tw5 restriction maps revealed the following. (i) The H-2K regions of both t-haplotypes retain a very similar molecular organization to that reported for B10, BALB/c and AKR. The nucleotide sequence diversity estimated from restriction site polymorphism is 0.68% between the t12 and tw5 haplotypes; these two t-haplotypes are no more similar to one another than BALB/c is to AKR. (ii) Genetic recombination is strongly implicated in generating H-2 polymorphism. (iii) Genetic polymorphisms, defined as small restriction fragment size differences, are observed at multiple sites along the H-2K region. An Alu-like B2 sequence and BAM5-R homologous sequence were identified as the inserted/deleted DNA segments of two of these sites, suggesting that insertion/deletion of mobile elements is a general mechanism for generating genetic diversity.

Animals↗