Transcriptional activation of mouse retrotransposons in vivo: specific expression in steroidogenic cells in response to trophic hormones.

Schiff, Rachel; Itin, Ahuva

doi:10.1101/gad.5.4.521

Cited by 38 publications

(37 citation statements)

References 36 publications

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“…The steroid biosynthetic pathway is activated in steroidogenic tissues of the ovary, testis, adrenal cortex, placenta, and corpus luteum by pituitary hormones (9, 10), which concomitantly induce synthesis of mVL30 RNA in these tissues (12,13). A key step in steroid synthesis is expression of P450scc, which is repressed by the binding of PSF to the IGFRE motif in the gene (5) and induced by IGF1 and mVL30 RNA.…”

Section: Discussionmentioning

confidence: 99%

“…A seminal finding was the concomitant induction of mVL30 RNA by pituitary hormones in mouse steroidogenic cells and Y1 cells (12,13), suggesting a role for mVL30 RNA in regulating steroid synthesis. According to the proposed regulatory mechanism, mVL30 RNA can induce one or more genes in the steroidogenic pathway by forming a complex that releases PSF from the genes.…”

Section: Regulation Of Steroid Synthesis In Micementioning

confidence: 99%

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Binding of mouse VL30 retrotransposon RNA to PSF protein induces genes repressed by PSF: Effects on steroidogenesis and oncogenesis

Sui

Garen

2004

Proc. Natl. Acad. Sci. U.S.A.

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We describe a mechanism of gene regulation involving formation of a complex between PSF protein and mouse VL30 (mVL30) retrotransposon RNA. PSF represses transcription of the insulin-like growth factor 1 (IGF1)-inducible gene P450scc by binding to an insulin-like growth factor response element (IGFRE) motif in the gene. The complex with mVL30 RNA releases PSF, allowing transcription to proceed. Retrovirally mediated transmission of mVL30 RNA to human tumor cells induced several genes, including oncogenes, which also are induced by IGF1, and promoted metastasis. In mice, steroid synthesis is activated in steroidogenic cells by pituitary hormones, which concomitantly induce transcription of mVL30 RNA in the cells. We showed that steroid synthesis could also be activated in mouse steroidogenic adrenal cells by transfection with cDNA encoding either mVL30 RNA tracts that form a complex with PSF or a small interfering RNA (siRNA) that degrades PSF transcripts. These results suggest that mVL30 RNA regulates steroidogenesis, and possibly other physiological processes of mice, by complex formation with PSF. Retrotransposons such as mVL30 apparently evolved not only as ''junk'' DNA but also as transcriptionally active noncoding DNA that acquired physiological and pathological functions. The complete genome of a mouse VL30 (mVL30) retrotransposon is structurally similar to a retroviral genome, with 5Ј and 3Ј LTRs flanking an internal region containing Ϸ3.7 kb (1). In contrast to the internal region of an infectious retroviral genome that encodes gag, pol, and env proteins, the corresponding region of the mVL30 genome has numerous stop codons in all reading frames that probably block formation of a functional protein. The mouse genome contains multiple copies of transcriptionally active mVL30 DNA, and virtually all mouse cells contain mVL30 RNA although the level varies among different tissues and at different developmental stages (1). Because retroviral vectors for gene transfer and gene therapy usually are produced in packaging cells derived from mouse cells, these cells also contain mVL30 RNA. A remarkable property of retroviral vectors is the capacity to transmit mVL30 RNA from a packaging cell to cells infected by the retrovirus, which synthesize, integrate, and transcribe mVL30 cDNA (1). In an earlier report (2), we showed that retroviral-mediated transfection of tissue factor (TF) cDNA into a nonmetastatic human melanoma cell line increased the metastatic potential of the cells to which mVL30-1 RNA also had been transmitted. The increase in metastatic potential depended on expression of TF protein on the cell surface and also on transcription of mVL30-1 cDNA. Dependence on mVL30-1 RNA was surprising because the RNA seems to lack significant coding potential. Here, we report that mVL30-1 RNA forms a complex with PSF, a multifunctional regulatory protein that binds to RNA in spliceosomes (3, 4) and to an IGFRE motif in the insulin-like growth factor 1 (IGF1)-inducible gene P450ssc that represses transcription of the g...

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Section: Discussionmentioning

confidence: 99%

Section: Regulation Of Steroid Synthesis In Micementioning

confidence: 99%

Binding of mouse VL30 retrotransposon RNA to PSF protein induces genes repressed by PSF: Effects on steroidogenesis and oncogenesis

Sui

Garen

2004

Proc. Natl. Acad. Sci. U.S.A.

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“…RL elements are known in a wide variety of organisms, including yeast (3)(4)(5), dipterans (6), lepidopterans (7), gymnosperms (8), angiosperms (9)(10)(11), and vertebrates, where they are recognized as retroviruses or endogenous retroviruses and sometimes as retrotransposons (12). RL elements are apparently widely distributed among echinoids.…”

mentioning

confidence: 99%

Retroviral-like element in a marine invertebrate.

Springer

Davidson

Britten

1991

Proc. Natl. Acad. Sci. U.S.A.

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Retroviral-like elements (RL elements) include retroviruses and long terminal repeat (LTR)-containing retrotransposons. We report the presence of sea urchin RL elements (termed SURL) in eight species of sea urchins and find that these RL elements belong to several subfamilies. The complete DNA sequence of one SURL element in Tripneustes grailla is 5266 base pairs long, including 254-nucleotide-long identical long terminal repeats (LTRs) (RT), and DNA copies of transcripts are inserted into the host genome. Together, LTR-containing retrotransposons and retroviruses are conveniently termed "retroviral-like elements" (RL elements) (2).RL elements are known in a wide variety of organisms, including yeast (3-5), dipterans (6), lepidopterans (7), gymnosperms (8), angiosperms (9-11), and vertebrates, where they are recognized as retroviruses or endogenous retroviruses and sometimes as retrotransposons (12). RL elements are apparently widely distributed among echinoids. We have observed the RT gene coding region of RL elements in the DNA of all sea urchin species that we have examined, including one cidaroid (Eucidaris tribuloides) and seven euechinoids (Strongylocentrotus purpuratus, Strongylocentrotusfranciscanus, Strongylocentrotus drobachiensis, Tripneustes gratilla, Lytechinus pictus, Lytechinus variegatus, and Arbacia punctulata).In early work on long, interspersed, repeated DNA of sea urchins, electron micrographic examination of reassociated DNA heteroduplexes revealed elements (called cs2108) that were about 5.2 kilobases (kb) long and had an interesting family and subfamily pattern (13). The elements are now named sea urchin RL elements (SURL elements). There are -400 copies of the RT gene coding region interspersed in the genome ofS. purpuratus (13,14). Cloned elements are named as in the example SURL1-21 (Sp), where the number 1 defines the SURL subfamily, 21 is an arbitrary label for the individual clone, and the letters in parentheses are the acronym of the species from which it was derived.Earlier data (13, 14) and our recent work (unpublished data) indicate that the SURL element family consists of subfamilies. Each subfamily contains from a few to 50 members (13). The subfamilies have been distinguished by the DNA sequence divergence of a conserved segment of the RT gene coding region. Members of each subfamily have closely similar sequences (1-10% divergent), whereas this DNA sequence region of each subfamily is greatly divergent from that of other subfamilies (30-45%). Interestingly, examples of intermediate divergence (10-30%) are rare or nonexistent. The implication is that copies of the RL elements that have been inserted into the genome drift in sequence, and the observation of stop codons in required coding regions suggests that many pseudogenes or "pseudocopies" are present. A similar pattern (termed superfamily and families) has been observed for the Ta elements of Arabidopsis (10) that are similar to copia of Drosophila (15). However, these elements are less similar to retroviruses tha...

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“…Ostrowski, unpubl.). In addition, the sequences of other independently derived VL30 elements have been reported (e.g., Itin and Keshet 1986;Schiff et al 1991). Their analysis reveals that individual VL30 elements contain many single-base differences in the R region; even closely related elements that are reg- Figure 1.…”

Section: The Nvl3 Ras-responsive Element Is Activated In V-fins-transmentioning

confidence: 99%

“…The upper arrow designates the 483-base undigested NVL3 probe; the lower arrow indicates the 221-base protected fragment. ulated in a similar fashion have many single-base differences in this region (Schiff et al 1991). Therefore, the LTRs of individual VL30 elements are sufficiently divergent that they would be distinguished by the stringent S 1 assay conditions used for the experiments reported here.…”

Section: The Nvl3 Ras-responsive Element Is Activated In V-fins-transmentioning

confidence: 99%

The carboxy-terminal catalytic domain of the GTPase-activating protein inhibits nuclear signal transduction and morphological transformation mediated by the CSF-1 receptor.

Bortner

Ulivi²,

Roussel³

et al. 1991

Genes Dev.

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To determine whether ras p21 products are necessary for signal transduction mediated by the colony stimulating factor-1 receptor (CSF-1R, the c-fins proto-oncogene product), we determined whether CSF-1R and ras activate a common nuclear target and whether the interruption of ras action affects CSF-1R signal transduction. Expression of the NVL3 retrotransposon was activated to the same extent in NIH-3T3 cells by both ras and v-fins oncogenes, and the ras-responsive element located in the long terminal repeat of NVL3 was demonstrated to be a common target for oncogene action. Human recombinant CSF-1 stimulated expression of the NVL3 element 30-fold in NIH-3T3 cells that contained human CSF-1R. Expression of the carboxy-terminal 374 amino acid residues of the human ras GTPase-activating protein (GAP) in cells containing CSF-1R was able to inhibit CSF-1 induction of NVL3 expression by 90%. Expression of the catalytic domain of GAP was also able to suppress transformation by either v-fins or ligand-activated CSF-1R. Expression of the c-jun proto-oncogene was activated by CSF-1R but was insensitive to the action of the catalytic domain of GAP. These results provide genetic evidence that in NIH-3T3 cells, ras p21 is involved in signal transduction mediated by CSF-1R.

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Transcriptional activation of mouse retrotransposons in vivo: specific expression in steroidogenic cells in response to trophic hormones.

Cited by 38 publications

References 36 publications

Binding of mouse VL30 retrotransposon RNA to PSF protein induces genes repressed by PSF: Effects on steroidogenesis and oncogenesis

Binding of mouse VL30 retrotransposon RNA to PSF protein induces genes repressed by PSF: Effects on steroidogenesis and oncogenesis

Retroviral-like element in a marine invertebrate.

The carboxy-terminal catalytic domain of the GTPase-activating protein inhibits nuclear signal transduction and morphological transformation mediated by the CSF-1 receptor.

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