Target sites for the transposition of rat long interspersed repeated DNA elements (LINEs) are not random

Furano, Anthony V.; Somerville, Charles C.; Tsichlis, Philip N.; D’Ambrosio, Ettoré

doi:10.1093/nar/14.9.3717

Cited by 45 publications

(16 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Usually, LINEs are termed silent "fossil DNA" without transcriptional potential and are widely used as markers in genetic and phylogenetic studies [52]. However, several studies have reported functional features of the LINE elements [46,47,53], including a strong association with apoptosis. The relevance of these DNA elements in beta cell destruction is at present unknown, and it cannot be ruled out that our findings represent a clone-specific phenomenon.…”

Section: Discussionmentioning

confidence: 99%

Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1?-mediated toxicity through inhibition of multiple nuclear factor-?B-regulated proapoptotic pathways

et al. 2004

View full text Add to dashboard Cite

Aims/hypothesis. The proinflammatory cytokine IL-1β induces apoptosis in pancreatic beta cells via pathways dependent on nuclear factor-κB (NF-κB), mitogen-activated protein kinase, and protein kinase C. We recently showed suppressor of cytokine signalling (SOCS)-3 to be a natural negative feedback regulator of IL-1β-and IFN-γ-mediated signalling in rat islets and beta cell lines, preventing their deleterious effects. However, the mechanisms underlying SOCS-3 inhibition of IL-1β signalling and prevention against apoptosis remain unknown. Methods. The effect of SOCS-3 expression on the global gene-expression profile following IL-1β exposure was microarray-analysed using a rat beta cell line (INS-1) with inducible SOCS-3 expression. Subsequently, functional analyses were performed. Results. Eighty-two known genes and several expressed sequence tags (ESTs) changed expression level 2.5-fold or more in response to IL-1β alone. Following 6 h of IL-1β exposure, 23 transcripts were upregulated. Of these, several, including all eight transcripts relating to immune/inflammatory response pathways, were suppressed by SOCS-3. Following 24 h of IL-1β exposure, secondary response genes were detected, affecting metabolism, energy generation, protein synthesis and degradation, growth arrest, and apoptosis. The majority of these changes were prevented by SOCS-3 expression. Multiple IL-1β-induced NF-κB-dependent proapoptotic early response genes were inhibited by SOCS-3 expression, suggesting that SOCS-3 inhibits NF-κB-mediated signalling. These observations were experimentally confirmed in functional analyses. Conclusions/interpretation. This study suggests that there is an unexpected cross-talk between the SOCS/ IFN and the IL-1β pathways of signalling in pancreatic beta cells, which could lead to a novel perspective of blocking two important proapoptotic pathways in pancreatic beta cells by influencing a single signalling molecule, namely SOCS-3.

show abstract

Section: Discussionmentioning

confidence: 99%

Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1?-mediated toxicity through inhibition of multiple nuclear factor-?B-regulated proapoptotic pathways

et al. 2004

View full text Add to dashboard Cite

show abstract

“…On the assumption that the 3' ends of all CR1 elements are indeed defined by the tandem octamers, it follows that target site preference may be a general feature of CR1 transpositions since, as noted above, a 20-bp window of modest sequence homology is apparent just downstream of the octamer repeat for the various CR1 elements (10). Preferred target sites have also been noted for other transposable elements (5,11,20).…”

mentioning

confidence: 85%

Evidence that chicken CR1 elements represent a novel family of retroposons.

Silva¹,

Burch²

1989

Mol. Cell. Biol.

View full text Add to dashboard Cite

We report the first precise delineation of a chicken CR1 element and show that it is flanked by a 6-base-pair target site duplication that occurred when this repetitive element transposed. The 3' end of this CRI element is defined by an 8-base-pair imperfect direct repeat, and we infer that this sequence represents the 3' end of all intact CR1 elements. In contrast, the 5' ends are not unique, and we argue that this variation existed at the time each element transposed. We also provide evidence that CR1 elements transposed into preferred target sites. CR1 elements therefore appear to represent a novel class of passive retroposons.

show abstract

“…First, while most non-LTR retrotransposable elements end in a short poly(A) sequence, very few of these elements contain the appropriately positioned AAU AAA (or AUUAAA) sequence upstream of this tail to promote the cleavage and polyadenylation steps (33). Second, some of the poly(A) tails found at the 3Ј end of integrated copies are interrupted by other nucleotides that are difficult to explain by the random mutation of a poly(A) tail after insertion (18). Third, some non-LTR elements end in repeating units other than poly(A).…”

mentioning

confidence: 99%

RNA Template Requirements for Target DNA-Primed Reverse Transcription by the R2 Retrotransposable Element

Luan

Eickbush

1995

Molecular and Cellular Biology

199

186

View full text Add to dashboard Cite

R2 is a non-long terminal repeat-retrotransposable element that inserts specifically in the 28S rRNA gene of most insects. The single protein encoded by R2 has been shown to contain both site-specific endonuclease and reverse transcriptase activities. Integration of the element involves cleavage of one strand of the 28S target DNA and the utilization of the exposed 3 hydroxyl group to prime the reverse transcription of the R2 RNA transcript. We have characterized the RNA requirement of this target DNA-primed reverse transcription reaction and found that the 250 nucleotides corresponding to the 3 untranslated region of the R2 transcript were necessary and sufficient for the reaction. To investigate the sequence requirements at the site of reverse transcription initiation, a series of RNA templates that contained substitutions and deletions at the extreme 3 end of the RNA were tested. The R2 templates used most efficiently had 3 ends which corresponded to the precise boundary of the R2 element with the 28S gene found in vivo. Transcripts containing short polyadenylated tails (8 nucleotides) were not utilized efficiently. R2 RNAs that were truncated at their 3 ends by 3 to 6 nucleotides were used less efficiently as templates and then only after the R2 reverse transcriptase had added extra, apparently nontemplated, nucleotides to the target DNA. The ability of the reverse transcriptase to add additional nucleotides to the target DNA before engaging the RNA template might be a mechanism for the generation of poly(A) or simple repeat sequences found at the 3 end of most non-long terminal repeatretrotransposable elements.Retrotransposable elements can be divided into two distinct groups on the basis of the presence or absence of terminal repeats and the nature of their encoded proteins (4,12,36,39,40). The first group to be identified consists of those elements that are flanked by long terminal repeats (LTR) and encode retrovirus-like gag and pol open reading frames. In agreement with their close structural similarity to retroviruses, all data on how this group of retrotransposable elements insert into eukaryotic genomes are consistent with a retrovirus-like mechanism (3, 30, 37). Indeed some LTR retrotransposable elements encode env-like genes and share certain transmission properties with retroviruses (23, 32).The second group of retrotransposable elements to be identified are not flanked by terminal repeats. A reverse transcriptase domain is the only homology that can be consistently identified for these elements (15). We will use the term non-LTR retrotransposable elements to identify this second group of elements (39). It has been demonstrated that these elements undergo retrotransposition by the removal of intron sequences during the generation of new copies (16,22,28). However, the absence both of LTRs and of an encoded integrase domain strongly suggests that these elements use a fundamentally different mechanism for their retrotransposition than that of the LTR-containing retrotransposable elements.Direct bioc...

show abstract

Target sites for the transposition of rat long interspersed repeated DNA elements (LINEs) are not random

Cited by 45 publications

References 30 publications

Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1?-mediated toxicity through inhibition of multiple nuclear factor-?B-regulated proapoptotic pathways

Suppressor of cytokine signalling (SOCS)-3 protects beta cells against IL-1?-mediated toxicity through inhibition of multiple nuclear factor-?B-regulated proapoptotic pathways

Evidence that chicken CR1 elements represent a novel family of retroposons.

RNA Template Requirements for Target DNA-Primed Reverse Transcription by the R2 Retrotransposable Element

Contact Info

Product

Resources

About