Functional endogenous LINE-1 retrotransposons are expressed and mobilized in rat chloroleukemia cells

Kirilyuk, Alexander; Tolstonog, Genrich V.; Damert, Annette; Held, Ulrike; Hahn, Silvia; Löwer, Roswitha; Buschmann, Christian; Horn, Axel V.; Traub, Peter; Schumann, Gerald G.

doi:10.1093/nar/gkm1045

Cited by 41 publications

(45 citation statements)

References 80 publications

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“…Like ORF2p, it shows a remarkable cis preference, that is, it associates preferentially with its encoding transcript (15,16). L1ORF1p can be localized in the cytoplasm (in putative stress granules) as well as in the nucleus (17,18) and can also be identified in large L1 ribonucleoprotein particles (RNPs) fractionated from cytoplasmic extracts (16,19,20).…”

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confidence: 99%

Non-LTR retrotransposons encode noncanonical RRM domains in their first open reading frame

Khazina

Weichenrieder

2009

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

135

200

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Non-LTR retrotransposons (NLRs) are a unique class of mobile genetic elements that have significant impact on the evolution of eukaryotic genomes. However, the molecular details and functions of their encoded proteins, in particular of the accessory ORF1p proteins, are poorly understood. Here, we identify noncanonical RNA-recognitionmotifs (RRMs) in several phylogenetically unrelated NLR ORF1p proteins. This provides an explanation for their RNA-binding properties and clearly shows that they are not related to the retroviral nucleocapsid protein Gag, despite the frequent presence of CCHC zinc knuckles. In particular, we characterize the ORF1p protein of the human long interspersed nuclear element 1 (LINE-1 or L1). We show that L1ORF1p is a multidomain protein, consisting of a coiled coil (cc), RRM, and C-terminal domain (CTD). Most importantly, we solved the crystal structure of the RRM domain, which is characterized by extended loops stabilized by unique salt bridges. Furthermore, we demonstrate that L1ORF1p trimerizes via its N-terminal cc domain, and we suggest that this property is functionally important for all homologues. The formation of distinct complexes with singlestranded nucleic acids requires the presence of the RRM and CTD domains on the same polypeptide chain as well as their close cooperation. Finally, the phylogenetic analysis of mammalian L1ORF1p shows an ancient origin of the RRM domain and supports a modular evolution of NLRs.genome evolution ͉ LINE-1 ͉ nucleic acid chaperone ͉ RNP ͉ crystal structure

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mentioning

confidence: 99%

Non-LTR retrotransposons encode noncanonical RRM domains in their first open reading frame

Khazina

Weichenrieder

2009

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

135

200

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“…When CHL cells are allowed to grow undisturbed in a confined space, genomic long interspersed nuclear element (LINE) sequences are transcriptionally spontaneously activated at relatively low cellularity, later resulting in the retrotransposition of LINE sequences and population death. 8,9 These findings have been confirmed by Kirilyuk & Tolstonog et al, 10 who also identified a functional LINE retrotransposon from a pool of CHL cell cDNAs. They determined the activity of this retrotransposon in HeLa and CHL cells, demonstrating its mobilization in CHL cells.…”

Section: Introductionmentioning

confidence: 62%

“…[8][9][10] Mathematical modelling and growth curve analysis was inferred as described below. In an undisturbed culture in a confined space, CHL cell growth can be accurately simulated (correlation coefficient r = .9957)…”

Section: Growth Curve Analysismentioning

confidence: 99%

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Spontaneous death of rat chloroleukaemia cells induced by an endogenous growth inhibitor

Rytömaa

Grip‐Rytömaa²

2017

Cell Proliferation

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Objectives: When rat chloroleukaemia (CHL) cells are grown undisturbed in a confined space, a genomic long interspersed nuclear element (LINE) is transcriptionally activated at a relatively low population density, followed by the retrotransposition of LINE and population death. This death programme is fundamentally different from conventional cell death pathways. Materials and methods:This work is essentially based on the re-analysis of relevant, old experimental data. Elemental analysis of a highly purified, long-stored inhibitor sample was performed. Genomic sequence searches were performed using the basic local alignment search tool (BLAST). Results: This death programme is initiated by an endogenous inhibitor secreted by CHL cells. The inhibitor is almost certainly identical to the pentapeptide pyroGlu-Glu-Asp-Cys-Lys, shown to be a cell line-specific inhibitor of normal granulocytic cells.The inhibitor is derived from a highly conserved short open reading frame in mammalian genomes. Conclusions:Although spontaneous population death may be a biological oddity restricted to rat CHL cells, we suggest that this death programme is responsible for the eradication of cancer cells following treatment with an inhibitor administered exogenously.

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“…Indeed, a functional L1 retrotransposon has been identified in rat chloroleukemia cells (Servomaa and Rytomaa 1990;Kirilyuk et al 2008). Furthermore, elements identified in silico might add to the list of potentially active ERVs (Baillie et al 2004;Gibbs et al 2004).…”

Section: à6mentioning

confidence: 99%

A novel active endogenous retrovirus family contributes to genome variability in rat inbred strains

Wang

Liška²,

Gösele³

et al. 2009

Genome Res.

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Endogenous retroviruses (ERVs) contribute to a range of germline, as well as somatic mutations in mammals. However, autonomous retrotransposition of potentially active elements has not been demonstrated in the rat genome. We cloned an insertion that disrupted the normal splicing of the Cntrob gene that was subsequently identified as a nonautonomous, novel endogenous retrovirus of the RnERV-K8e family. The RnERV-K8e family is closely related to the recently reported MmERV-K10c elements, but differs from the autonomous mouse MusD or IAP families. In addition, we identified a novel, unexpectedly close relative of RnERV-K8e in the mouse, suggesting ERV-K cross-species transmission between mice and rats. We cloned a potentially autonomous RnERV-K8e element identified by in silico analysis and, using an in vitro retrotransposition assay, demonstrated that it is capable of retrotransposition. This particular element (named Rat-r, pronounced ''retro'') encodes a retroviral envelope gene (env); however, env is not required for de novo retrotransposition events. Significant levels of RnERV-K8e-associated genetic polymorphisms were detected among inbred rat strains, suggesting ongoing retrotransposition in the rat genome. This study identifies an ERV-K-type family in rats that shows obvious signs of recent activity. Ongoing retrotranspositional activity may significantly add to genomic variability among inbred rat strains.

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Functional endogenous LINE-1 retrotransposons are expressed and mobilized in rat chloroleukemia cells

Cited by 41 publications

References 80 publications

Non-LTR retrotransposons encode noncanonical RRM domains in their first open reading frame

Non-LTR retrotransposons encode noncanonical RRM domains in their first open reading frame

Spontaneous death of rat chloroleukaemia cells induced by an endogenous growth inhibitor

A novel active endogenous retrovirus family contributes to genome variability in rat inbred strains

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