The Long Terminal Repeat of an Endogenous Retrovirus Induces Alternative Splicing and Encodes an Additional Carboxy-Terminal Sequence in the Human Leptin Receptor

Kapitonov, Vladimir V.; Jurka, Jerzy

doi:10.1007/pl00013153

Cited by 67 publications

(42 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The insertion of transposable elements in or near introns can result in alternative splicing patterns. Such events are also believed to have contributed to gene evolution (e.g., Kapitonov and Jurka 1999). The insertion of transposable elements into the coding region of genes is typically associated with loss of gene function (Green 1988).…”

Section: Cer Elements May Contribute To C Elegans Gene Structure Andmentioning

confidence: 99%

Evolutionary History of Cer Elements and Their Impact on the C. elegans Genome

Ganko¹,

Fielman²,

McDonald³

2001

Genome Res.

View full text Add to dashboard Cite

We report the results of sequence analysis and chromosomal distribution of all distinguishable long terminal repeat (LTR) retrotransposons (Cer elements) in the Caenorhabditis elegans genome. Included in this analysis are all readily recognizable full-length and fragmented elements, as well as solo LTRs. Our results indicate that there are 19 families of Cer elements, some of which display significant subfamily structure. Cer elements can be clustered based on their tRNA primer binding sites (PBSs). These clusters are in concordance with our reverse transcriptase-and LTR-based phylogenies. Although we find that most Cer elements are located in the gene depauperate chromosome ends, some elements are located in or near putative genes and may contribute to gene structure and function. The results of RT-PCR analyses are consistent with this prediction.

show abstract

Section: Cer Elements May Contribute To C Elegans Gene Structure Andmentioning

confidence: 99%

Evolutionary History of Cer Elements and Their Impact on the C. elegans Genome

Ganko¹,

Fielman²,

McDonald³

2001

Genome Res.

View full text Add to dashboard Cite

show abstract

“…HERV-E also appears to be involved in the expression of human pleiotrophin in placenta (12). It has also been demonstrated that a HERV-K LTR encodes the last 67 amino acids of one form of the leptin receptor OBR (13). These findings indicate that an LTR insertion adjacent to or within a gene could have a variety of effects without destroying gene function.…”

mentioning

confidence: 95%

Long Terminal Repeats Are Used as Alternative Promoters for the Endothelin B Receptor and Apolipoprotein C-I Genes in Humans

Medstrand

Landry

Mager

2001

Journal of Biological Chemistry

189

126

View full text Add to dashboard Cite

To examine the potential regulatory involvement of retroelements in the human genome, we screened the transcribed sequences of GenBank TM and expressed sequence tag data bases with long terminal repeat (LTR) elements derived from different human endogenous retroviruses. These screenings detected human transcripts containing LTRs belonging to the human endogenous retrovirus-E family fused to the apolipoprotein CI (apoC-I) and the endothelin B receptor (EBR) genes. However, both genes are known to have non-LTR (native) promoters. Initial reverse transcription-polymerase chain reaction experiments confirmed and authenticated the presence of transcripts from both the native and LTR promoters. Using a 5-rapid amplification of cDNA ends protocol, we showed that the alternative transcripts of apoC-I and EBR are initiated and promoted by the LTRs. The LTR-apoC-I fusion and native apoC-I transcripts are present in many of the tissues tested. As expected, we found apoC-I preferentially expressed in liver, where about 15% of the transcripts are derived from the LTR promoter. Transient transfections suggest that the expression is not dependent on the LTR itself, but the presence of the LTR increases activity of the apoC-I promoter from both humans and baboons. The native EBR-driven transcripts were also detected in many tissues, whereas the LTR-driven transcripts appear limited to placenta. In contrast to the LTR of apoC-I, the EBR LTR promotes a significant proportion of the total EBR transcripts, and transient transfection results indicate that the LTR acts as a strong promoter and enhancer in a placental cell line. This investigation reports two examples where LTR sequences contribute to increased transcription of human genes and illustrates the impact of mobile elements on gene and genome evolution.

show abstract

“…Based on the given LTR mutation rate of 0.2-0.3 %, its greater than 15 % difference from other known LTRs suggests that it may be more than 50-75 million-years-old and therefore present in primates and possibly other mammalian annexin A5 genes. The contribution of LTRs as structural mutagens and donors of functional DNA elements for transcription factor binding, such as c-myb [47] or steroids [48], could directly impinge on annexin A5 regulation (Figure 2), although the in i o relevance of specific domains must be assessed under defined conditions. The prospect that human annexin A5 transcription is subject to retroviral repressor element(s) (Figure 3) is a concrete example of symbiotic co-evolution at the molecular level, and a potentially major modulator during cell cycling, tissue differentiation or changed cellular environment.…”

Section: Discussionmentioning

confidence: 99%

Functional analysis of the human annexin A5 gene promoter: a downstream DNA element and an upstream long terminal repeat regulate transcription

Carcedo

Iglesias

Bances

et al. 2001

Biochemical Journal

View full text Add to dashboard Cite

Human annexin A5 is a ubiquitous protein implicated in diverse signal transduction processes associated with cell growth and differentiation, and its gene regulation is an important component of this function. Promoter transcriptional activity was determined for a wide 5′ portion of the human annexin A5 gene, from bp −1275 to +79 relative to the most 5′ of several discrete transcription start points. Transfection experiments carried out in HeLa cells identified the segment from bp −202 to +79 as the minimal promoter conferring optimal transcriptional activity. Two canonical Sp1 sites in the immediate 5′ flanking region of a CpG island were required for significant transcription. Strong repressive activity in the distal promoter region between bp −717 to −1153 was attributed to the presence of an endogenous retroviral long terminal repeat, homologous with long terminal repeat 47B. The downstream sequence from bp position +31 to +79 in untranslated exon 1 was also essential for transcription, as its deletion from any of the plasmid constructs abolished activity in transfection assays. Electrophoretic mobility-shift assays, Southwestern-blot analysis and affinity chromatography were used to identify a protein doublet of relative molecular mass 35kDa that bound an octanucleotide palindromic sequence in exon 1. The DNA cis-element resembled an E-box, but did not bind higher molecular mass transcription factors, such as upstream stimulatory factor or activator protein 4. The discovery of a downstream element crucial for annexin A5 gene transcription, and its interaction with a potentially novel transcription factor or complex, may provide a clue to understanding the initiation of transcription by TATA-less, multiple start site promoters.

show abstract

The Long Terminal Repeat of an Endogenous Retrovirus Induces Alternative Splicing and Encodes an Additional Carboxy-Terminal Sequence in the Human Leptin Receptor

Cited by 67 publications

References 27 publications

Evolutionary History of Cer Elements and Their Impact on the C. elegans Genome

Evolutionary History of Cer Elements and Their Impact on the C. elegans Genome

Long Terminal Repeats Are Used as Alternative Promoters for the Endothelin B Receptor and Apolipoprotein C-I Genes in Humans

Functional analysis of the human annexin A5 gene promoter: a downstream DNA element and an upstream long terminal repeat regulate transcription

Contact Info

Product

Resources

About