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At least 217 records · Page 12Linked to original sources
PubMed2003

Distribution of retroelements in centromeres and neocentromeres of maize.

Fluorescent in situ hybridization was used to examine the distribution of six abundant long terminal repeat (LTR) retroelements, Opie, Huck, Cinful-1, Prem-2/Ji, Grande, and Tekay/Prem-1 on maize pachytene chromosomes. Retroelement staining in euchromatin was remarkably uniform, even when we included the structurally polymorphic abnormal chromosome 10 (Ab10) in our analysis. This uniformity made it possible to use euchromatin as a control for quantitative staining intensity measurements in other regions of the genome. The data show that knobs, known to function as facultative neocentromeres when Ab10 is present, tend to exclude retroelements. A notable exception is Cinful-1, which accumulates in TR-1 knob arrays. Staining for each of the six retroelements was also substantially reduced in centromeric satellite arrays to an average of 30% of the staining in euchromatin. This contrasted with two previously described centromere-specific retrotransposable (CR) elements that were readily detected in centromeres. We suggest that retroelements are relatively rare in centromeres because they interrupt the long satellite arrays thought to be required for efficient centromere function. CR elements may have evolved mutualistic relationships with their plant hosts: they are known to interact with the kinetochore protein CENH3 and appear to accumulate in clusters, leaving long satellite arrays intact.

Centromere↗
PubMed1998

Replication errors during in vivo Ty1 transposition are linked to heterogeneous RNase H cleavage sites.

We previously identified a mutational hotspot upstream of the Ty1 U5-primer binding site (PBS) border and proposed a novel mechanism to account for this phenomenon during Ty1 replication. In this report, we verify key points of our model and show that in vivo RNase H cleavage of Ty1 RNA during minus-strand strong-stop synthesis creates heterogeneous 5' RNA ends. The preferred cleavage sites closest to the PBS are 6 and 3 bases upstream of the U5-PBS border. Minus-strand cDNA synthesis terminates at multiple sites determined by RNase H cleavage, and DNA intermediates frequently contain 3'-terminal sequence changes at or near their template ends. These data indicate that nontemplated terminal base addition during reverse transcription is a real in vivo phenomenon and suggest that this mechanism is a major source of sequence variability among retrotransposed genetic elements.

DNA Replication↗
PubMed2002

Chimeric RNA transposition intermediates of the I factor produce precise retrotransposed copies.

I elements in Drosophila melanogaster are non-long terminal repeat (LTR) retrotransposons of particular interest because high levels of transposition can be induced by appropriate crosses. They use a full-length RNA transposition intermediate as a template for reverse transcription. Detailed molecular characterization of this intermediate is rendered difficult because of the many transcripts produced by defective elements. The use of an active I element marked with a sequence encoding the HA epitope solves this problem. We used an RNA circularization procedure followed by RT-PCR to analyze the transcripts produced by actively transposing tagged I elements. Most start at the 5' end at the second nucleotide of the I element and all are polyadenylated at a site located in genomic sequences downstream of the 3' end. One of the tagged I elements, inserted in locus 88A, produces chimeric transcripts that carry sequences from both 5'- and 3'-flanking genomic DNA. We show that synthesis of these chimeric transcripts is controlled by the I element itself. Analysis of full-length transposed copies of this element shows that the extra sequences at the 5' and 3' ends are not integrated during retrotransposition. This suggests that initiation and arrest of reverse transcription during retrotransposition are precise processes.

3' Flanking Region↗
PubMed1998

An actively retrotransposing, novel subfamily of mouse L1 elements.

Retrotransposition of LINEs and other retroelements increases repetition in mammalian genomes and can cause deleterious mutations. Recent insertions of two full-length L1s, L1spa and L1Orl, caused the disease phenotypes of the spastic and Orleans reeler mice respectively. Here we show that these two recently retrotransposed L1s are nearly identical in sequence, have two open reading frames and belong to a novel subfamily related to the ancient F subfamily. We have named this new subfamily TF (for transposable) and show that many full-length members of this family are present in the mouse genome. The TF 5' untranslated region has promoter activity, and TF-type RNA is abundant in cytoplasmic ribonucleoprotein particles, which are likely intermediates in retrotransposition. Both L1spa and L1Orl have reverse transcriptase activity in a yeast-based assay and retrotranspose at high frequency in cultured cells. Together, our data indicate that the TF subfamily of L1s contains a major class of mobile elements that is expanding in the mouse genome.

Animals↗
PubMed2005

SINE extinction preceded LINE extinction in sigmodontine rodents: implications for retrotranspositional dynamics and mechanisms.

Short Interspersed Nuclear Elements, or SINEs, retrotranspose despite lacking protein-coding capability. It has been proposed that SINEs utilize enzymes produced in trans by Long Interspersed Nuclear Elements, or LINEs. Strong support for this hypothesis is found in LINE and SINE pairs that share sequence homology; however, LINEs and SINEs in primates and rodents are only linked by an insertion site motif. We have now profiled L1 LINE and B1 SINE activity in 24 rodent species including candidate taxa for the first documented L1 extinction. As expected, there was no evidence for recent activity of B1s in species that also lack L1 activity. However, B1 silencing appears to have preceded L1 extinction, since B1 activity is also lacking in the genus most closely related to those lacking active L1s despite the presence of active L1s in this genus. A second genus with active L1s but inactive B1s was also identified.

Animals↗
PubMed1996

The three human cytochrome P450 lanosterol 14 alpha-demethylase (CYP51) genes reside on chromosomes 3, 7, and 13: structure of the two retrotransposed pseudogenes, association with a line-1 element, and evolution of the human CYP51 family.

The three human lanosterol 14 alpha-demethylase (CYP51) genes have been mapped to human chromosomes 3, 7, and 13 using a polychromosomal somatic cell hybrid panel. Two of the genes have been cloned from human chromosome 3-specific (CYP51P1) or from human chromosome 13-containing (CYP51P2) cell hybrids. Both were found to be processed pseudogenes, the first reported in the cytochrome P450 (CYP) gene superfamily. The functional CYP51 gene resides on human chromosome 7. CYP51P1 is 96.5% identical to the human CYP51 coding sequence and is not interrupted with introns but has six in-frame stop codons resulting from point mutations. The intronless CYP51P2 gene is 97.2% identical to the CYP51 cDNA coding region. It has a 1-bp insertion leading to a change of reading frame after codon 9 and a stop codon after amino acid 81. In addition, the CYP51P2 sequence is interrupted with a 5' truncated 131-bp LINE-1 element after nucleotide 606. The element belongs to the youngest LINE subfamily Sb and is 98.2% identical to the LINE-1 element expressed in human teratocarcinoma cells. CYP51 processed pseudogenes are the only known examples of the reverse flow of genetic information during evolution of the large (more than 480 genes) CYP superfamily, suggesting expression in the germ line and a housekeeping function of the lanosterol 14 alpha-demethylase gene. CYP51 pseudogenes evolved by two independent reverse transcription events of the human CYP51 mRNA approximately 9.5 MYR (CYP51P2) and approximately 11.7 MYR (CYP51P1) ago and were inactivated soon after the insertion. The truncated L1 element was inserted into CYP51P2 approximately 6 MYR ago.

Amino Acid Sequence↗
PubMed1998

The impact of L1 retrotransposons on the human genome.

The 'master' human mobile element, the L1 retrotransposon, has come of age as a biological entity. Knowledge of how it retrotransposes in vivo, how its proteins act to retrotranspose other poly A elements and the extent of its role in shaping the human genome should emerge rapidly over the next few years. We review the impact of retrotransposons and how new insight is likely to lead to important practical applications for these intriguing mobile elements.

Genome, Human↗
PubMed2004

Retrotransposition of limited deletion type of intracisternal A-particle elements in the myeloid leukemia Clls of C3H/He mice.

The murine genome has about 1,000 copies of DNA elements for the intracisternal A-particle (IAP) that resembles a retrovirus. We previously reported that the genomic DNA of the cells from radiation-induced acute myeloid leukemia (AML) lines derived from C3H/He inbred mice was frequently rearranged by the integration of the IAP element. In this study, 8 IAP elements from the characteristic integration sites in 6 cell lines of radiation-induced AML from different mice were characterized and compared in structure with 114 IAP elements isolated from the normal C3H/He genome. One of the 8 elements was a full-length type I IAP, and 7 were of type-I Delta 1 with a common deletion site. Although the type I Delta 1 form is a minor population accounting for about 6% of total genomic IAP elements, it is predominantly retrotransposed in the AML cells from different C3H/He mice. This indicates that limited populations of the IAP elements contribute to the unique retrotransposition in AML cells.

Animals↗
PubMed2006

Life without GAG: the BARE-2 retrotransposon as a parasite's parasite.

A large proportion of the plant LTR (Long Terminal Repeat) retrotransposons are partly or completely unable to synthesize their own machinery for transposition. However, most of these inactive or non-autonomous elements are likely able to retrotranspose, based on their insertional polymorphism. Therefore, they must be parasitic on one or more active partners. Here, we describe the parasitism of the chimeric BARE-2 element on the active BARE-1 (Barley RetroElement-2 and -1 respectively). These two elements are present in the Triticeae and related species, and are together polymorphic among closely related accessions. BARE-2 elements are unable to synthesize their own GAG protein, and harbor a specific ATG deletion in the gag ORF. However, BARE-2 sequences are conserved with BARE-1 in the PBS (Primer Binding Site), PSI (Packaging SIgnal) and DIS (DImerization Signal) domains. As these motifs have been shown to allow parasitism among the lentiviruses, we conclude that BARE-2 is probably a partial parasite of the BARE-1 element because the machinery of the latter can complement the defective GAG of the former. This example emphasizes that we must characterize the parasitic network of LTR retrotransposons and its implication for integration of autonomous, inactive, and non-autonomous elements in order to understand current and past host genome evolution.

Base Sequence↗
PubMed2003

Template jumping by a LINE reverse transcriptase has created a SINE-like 5S rRNA retropseudogene in Dictyostelium.

Short interspersed nuclear elements (SINEs) are non-autonomous retroelements that mimic the 3' ends of so-called long interspersed nuclear elements (LINEs) to ensure their propagation by proteins encoded by autonomous LINEs. The Dictyostelium discoideum genome contains a family of LINE-like retrotransposons that specifically target tRNA genes for integration (TRE elements). We describe here a retrotransposed ribosomal 5S RNA pseudogene in the D. discoideum genome that contains at its 3' end an 8-bp sequence derived from the 3' end of a TRE and a polyadenine tail. The r5S "retropseudogene" is flanked by target-site duplications that are characteristic for TREs, and is inserted upstream of a tRNA gene, just like a typical TRE. The D. discoideum r5S retropseudogene has structural features of a SINE, but has not been amplified, probably due to the 5'-truncation that occurred upon its initial retrotransposition. The discovery of this D. discoideum r5S retropseudogene reveals that SINEs can be created de novo during reverse transcription of LINE transcripts, if the LINE-encoded reverse transcriptase dissociates from the LINE RNA and jumps to other cellular RNAs-particularly genes transcribed by RNA polymerase III-to create continuous mixed cDNAs.

Animals↗
PubMed2003

SVA elements are nonautonomous retrotransposons that cause disease in humans.

L1 elements are the only active autonomous retrotransposons in the human genome. The nonautonomous Alu elements, as well as processed pseudogenes, are retrotransposed by the L1 retrotransposition proteins working in trans. Here, we describe another repetitive sequence in the human genome, the SVA element. Our analysis reveals that SVA elements are currently active in the human genome. SVA elements, like Alus and L1s, occasionally insert into genes and cause disease. Furthermore, SVA elements are probably mobilized in trans by active L1 elements.

Base Sequence↗
PubMed2003

A novel family of tRNA-derived SINEs in the colugo and two new retrotransposable markers separating dermopterans from primates.

Short interspersed nuclear elements (SINEs) provide a near homoplasy free and copious source of molecular evolutionary markers with precisely defined character polarity. Used as molecular cladistic markers in presence/absence analyses, they represent a powerful complement to phylogenetic reconstructions that are based on sequence comparisons on the level of nucleotide substitutions. Recent sequence comparisons of large data sets incorporating a broad eutherian taxonomic sample have led to considerations of the different primate infraorders to constitute a paraphyletic group. Statistically significant support against the monophyly of primates has been obtained by clustering the flying lemur-also termed colugo-(Cynocephalus, Dermoptera) amidst the primates as the sister group to anthropoid primates (New World monkeys, Old World monkeys, and hominoids). We discovered retrotransposed markers that clearly favor the monophyly of primates, with the markers specific to all extant primates but definitively absent at the orthologous loci in the flying lemur and other non-primates. By screening the colugo genome for phylogenetic informative SINEs, we also recovered a novel family of dermopteran specific SINE elements that we call CYN. This element is probably derived from the isoleucine tRNA and appears in monomeric, dimeric, and trimeric forms. It has no long tRNA unrelated region and no poly(A) linker between the monomeric subunits. The characteristics of the novel CYN-SINE family indicate a relatively recent history. Therefore, this SINE family is not suitable to solve the phylogenetic affiliation between dermopterans and primates. Nevertheless it is a valuable device to reconstruct the evolutionary steps from a functional tRNA to an interspersed SINE element.

Animals↗
PubMed1996

Mutation analysis in the BRCA2 gene in primary breast cancers.

Breast cancer, one of the most common and deleterious of all diseases affecting women, occurs in hereditary and sporadic forms. Hereditary breast cancers are genetically heterogeneous; susceptibility is variously attributable to germline mutations in the BRCA1 (ref. 1), BRCA2 (ref. 2), TP53 (ref. 3) or ataxia telangiectasia (ATM) genes, each of which is considered to be a tumour suppressor. Recently a number of germline mutations in the BRCA2 gene have been identified in families prone to breast cancer. We screened 100 primary breast cancers from Japanese patients for BRCA2 mutations, using PCR-SSCP. We found two germline mutations and one somatic mutation in our patient group. One of the germline mutations was an insertion of an Alu element into exon 22, which resulted in alternative splicing that skipped exon 22. The presence of a 64-bp polyadenylate tract and evidence for an 8-bp target-site duplication of the inserted DNA implied that the retrotransposal insertion of a transcriptionally active Alu element caused this event. Our results indicate that somatic BRCA2 mutations, like somatic mutations in the BRCA1 gene, are very rare in primary breast cancers.

BRCA2 Protein↗
PubMed1998

Recombination between subtypes creates a mosaic lineage of LINE-1 that is expressed and actively retrotransposing in the mouse genome.

LINE-1, or L1, elements are retrotransposons that have amplified to high-copy number during the evolution of mammals. L1 appears to amplify in waves, spawning large numbers of progeny such that elements with distinct sequence features dominate the dispersal process in a given window of time. This process generates discrete subfamilies of L1 within mammalian genomes, with the oldest being remnants, or fossils, of earlier waves of amplification. In mice, at least three distinct subfamilies of L1 were distinguished by their unique 5' ends, A, F and V. These subfamilies amplified at distinct times in the evolution of mice, with A being the youngest and V the oldest; both V and F subfamilies were believed extinct. Recent data established that a variant of the F family, TF, is actively retrotransposing. We demonstrate here that members of the TF subfamily are abundantly expressed in mouse cells and encode the major protein constituent of L1 ribonucleoprotein particles. Although members of the TF subfamily are not as numerous in the genomes of laboratory mice as are members of the older A and F subfamilies, they appear to have been activated some time ago during mouse evolution, in the common ancestor of Mus spretus and Mus domesticus. Phylogenetic analysis demonstrates that this modern, active form of TF-type L1 has a composite evolutionary history, showing evidence of multiple recombinations between distinct L1 variants, including members of the A and F subfamilies.

Animals↗
PubMed2002

Insertional polymorphisms of ETn retrotransposons include a disruption of the wiz gene in C57BL/6 mice.

ETn (early transposon) elements are moderate repetitive sequences present in hundreds of copies in the mouse genome. Their length ranges from 4.4 to 7.1 kb, and, like transposons, they contain long terminal repeats (LTRs) on both sides and are flanked by target site duplications (Kaghad et al. 1985). ETn-related elements can be grouped into three distinct families. Members of the ETn I and ETn II families mainly contain sequences of unknown origin in their core region. Only very short stretches of retrovirus-like sequences are present, and there are no ORFs. ETn I and ETn II elements differ primarily in the 3- half of both the 5- and 3- LTR, and in the 5- end of the core region (see Fig. 1). As a consequence, only ETn II elements contain a primer binding site for tRNALys. In contrast to ETn I and ETn II, members of the recently described MusD family (Mager and Freeman 2000) contain ORFs for (at least parts of) D-type virus Gag, Pro, and Pol proteins. However, in other regions they are structurally similar to ETn II elements and contain an intact primer binding site. It has been shown that MusD sequences are evolutionarily older than ETn II elements, suggesting that the latter might have arisen by recombinatory replacement of the MusD gene-coding sequences with sequences of unknown origin (Mager and Freeman 2000). ETn elements are still active as retrotransposons. In the past years, several germ line and somatic mutations caused by fresh ETn integrations have been found (Table 1). From 19 mutations, sufficient sequence is available in seven cases to show that the insertion was an ETn II element. In eight cases, the sequence data available indicate either an ETn II or a MusD element. ETn I has not been found to be the cause of any mutations, prompting the suggestion that ETn II is the "mobile" family, whereas ETn I elements have lost the capacity to retrotranspose.

Animals↗
PubMed1998

Rapid amplification of a retrotransposon subfamily is evolving the mouse genome.

Retrotransposition affects genome structure by increasing repetition and producing insertional mutations. Dispersion of the retrotransposon L1 throughout mammalian genomes suggests that L1 activity might be an important evolutionary force. Here we report that L1 retrotransposition contributes to rapid genome evolution in the mouse, because a number of L1 sequences from the T(F) subfamily are retrotransposition competent. We show that the T(F) subfamily is large, young and expanding, containing approximately 4,800 full-length members in strain 129. Eleven randomly isolated, full-length T(F) elements averaged 99.8% sequence identity to each other, and seven of these retrotransposed in cultured cells. Thus, we estimate that the mouse genome contains approximately 3,000 active T(F) elements, 75 times the estimated number of active human L1s. Moreover, as T(F) elements are polymorphic among closely related mice, they have retrotransposed recently, implying rapid amplification of the subfamily to yield genomes with different patterns of interspersed repetition. Our data show that mice and humans differ considerably in the number of active L1s, and probably differ in the contribution of retrotransposition to ongoing sequence evolution.

5' Untranslated Regions↗
PubMed2005

Identification and characterization of critical cis-acting sequences within the yeast Ty1 retrotransposon.

The yeast long terminal repeat (LTR) retrotransposon Ty1, like retroviruses, encodes a terminally redundant RNA, which is packaged into virus-like particles (VLPs) and is converted to a DNA copy by the process of reverse transcription. Mutations predicted to interfere with the priming events during reverse transcription and hence inhibit replication are known to dramatically decrease transposition of Ty1. However, additional cis-acting sequences responsible for Ty1 replication and RNA dimerization and packaging have remained elusive. Here we describe a modular mini-Ty1 element encoding the minimal sequence that can be retrotransposed by the Ty1 proteins, supplied in trans by a helper construct. Using a mutagenic screening strategy, we recovered transposition-deficient modular mini-Ty1-HIS3 elements with mutations in sequences required in cis for Ty1 replication and integration. Two distinct clusters of mutations mapped near the 5'-end of the Ty1 RNA. The clusters define a GAGGAGA sequence at the extreme 5'-end of the Ty1 transcript and a complementary downstream UCUCCUC sequence, 264 nt into the RNA. Disruption of the reverse complementarity of these two sequences decreased transposition and restoration of complementarity rescued transposition to wild-type levels. Ty1 cDNA was reduced in cells expressing RNAs with mutations in either of these short sequences, despite nearly normal levels of Ty1 RNA and VLPs. Our results suggest that the intramolecular interaction between the 5'-GAGGAGA and UCUCCUC sequences stabilizes an RNA structure required for efficient initiation of reverse transcription.

Base Sequence↗