Long Interspersed Nuclear Elements 1 (LINE1): The chimeric transcript L1-MET and its involvement in cancer

Cervantes-Ayalc, Andrea; Esparza‐Garrido, Ruth Ruiz; Velázquez-Flores, Miguel Ángel

doi:10.1016/j.cancergen.2019.11.004

Cited by 9 publications

(10 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the presence of these sequences along the human evolution has shaped the genome and new functional elements have been generated in most cases by a unique mechanism called retrotransposition [39]. Retrotransposition is the greatest remodeling force of the human genome, and it is currently represented by the Long Interspersed Nuclear Element 1 (LINE 1) [40][41][42][43]. These are 6-7kb elements that have all the machinery to be copied and mobilized into the genome.…”

Section: Mechanisms Of U6 Retrotranspositionmentioning

confidence: 99%

“…The intrinsic nature of LINE 1 is to be copied and inserted itself into the genome, increasing genomic instability. In response to this, the cell has 'engineered' many mechanisms that control the levels of LINE1 retrotransposition; alterations in these regulatory systems can increase the mobility of LINE-1 and promote the formation of chimeric genes; however, in the case of U6, the conundrum is why a large spread of U6 has been 'allowed' in the human genome [43].…”

Section: Mechanisms Of U6 Retrotranspositionmentioning

confidence: 99%

“…In the 80s, the first studies of snRNA pseudogenes formation showed 4 different classes among which, three classes could be formed by using RNA as intermediate [43][44][45][46][47]. Recent studies have redefined the snRNAs pseudogene formation classification based on their structure organization (Table 3) Doucet et al 2015 described in detail some processes by which LINE-1 elements can recruit RNA molecules, especially the U6 sequence, promoting diversification and propagation of these sequences in the genome, not only in humans, but also in different species; however, the largest number of inserted and scattered copies are found in the human genome [42].…”

Section: Mechanisms Of U6 Retrotranspositionmentioning

confidence: 99%

See 2 more Smart Citations

The Potential of U6 and Its Copies in the Regulation of the Human Genome

Velázquez-Flores¹,

Esparza‐Garrido²

2021

COR

View full text Add to dashboard Cite

Non-coding RNAs are conformed by a large repertoire of RNA molecules with unimaginable tridimensional structures and functions. Small nuclear RNAs are an essential part of the spliceosome machinery, which is crucial for proper mRNA maturation. It is important to add that U6, one of the four snRNAs forming the spliceosome has been extensively studied. Full-length U6 (U6-1) loci are widely dispersed throughout the genome (200-900 copies), but a few U6 full-length loci have been identified to date as potentially active genes. The importance of U6 to carry out, together with other snRNAs, the catalytic activity and recognition of annealing target sequences, its evolution in the genome and the fact that the genome has many U6 copies and pseudogenes, its association with retrotransposition, as well as their implication in diseases is discussed in this review.

show abstract

Section: Mechanisms Of U6 Retrotranspositionmentioning

confidence: 99%

Section: Mechanisms Of U6 Retrotranspositionmentioning

confidence: 99%

Section: Mechanisms Of U6 Retrotranspositionmentioning

confidence: 99%

See 1 more Smart Citation

The Potential of U6 and Its Copies in the Regulation of the Human Genome

Velázquez-Flores¹,

Esparza‐Garrido²

2021

COR

View full text Add to dashboard Cite

show abstract

“…The transposable elements that replicate within the host genome may contribute to somatic mosaicism and, thus potent regulatory polygenic modifications in the diseased state [186,187] play a role in the pathogenesis of inflammatory autoimmune Chagas disease [35,41,57,172,188]. In so far, the polygenic modifications involved in the genesis of cancer [189][190][191][192][193] have not been ascribed to any Ambiental factor inducer of the lateral exogenous kDNA transfer. In this regard, evolution is inherently opportunistic.…”

Section: Cross-kingdom Dna Transfer Evolution Natural Selection and Chagas Diseasementioning

confidence: 99%

The Trypanosoma cruzi kinetoplast DNA minicircle sequences transfer biomarker of the multidrug treatment of Chagas disease

Teixeira

Sousa

Gomes

et al. 2021

Preprint

View full text Add to dashboard Cite

BackgroundThe Trypanosoma cruzi infection renders the transfer of the mitochondrion kinetoplast DNA minicircle sequences into the host’s genome. The Aves are refractory to the infection, but chicks hatched from the T. cruzi inoculated eggs integrate the DNA minicircle sequences into the germ line cells. Rabbits, mice and chickens with the minicircle sequences mutations develop the Chagas cardiomyopathy and the DNA transfer underpins the heart disease.MethodologyThe PCR with the specific primer sets revealed the Protist nuclear DNA and the kinetoplast DNA in the agarose gels bands probed with the radiolabel specific sequences from tissues of the T. cruzi-infected rabbits and of the mice. A target- primer TAIL-PCR amplification employing primer sets from the chickens, rabbits and mice, in combination with primer sets from the the T. cruzi kinetoplast minicircle sequences was used. This approach led us to disclose the integration sites of the kinetoplast DNA biomarker, then, used to monitor the effect of multidrug treatment of the T. cruzi infected mice.Principal findingsThe Southern hybridization, clone and sequence of the amplification products revealed the DNA minicircle sequences integrations sites in the LINE transposable elements. An array of inhibitors of eukaryote cells division was used to arrest the DNA transfer. It was shown that nine out of 12 inhibitors prevented the kinetoplast DNA integration into the macrophage genome. The multidrug treatment of the acutely T. cruzi-infected mice with Benznidazole, Azidothymidine and Ofloxacin lessened circa 2.5-fold the rate of the minicircle sequences integrations in the mouse genome and inhibited the rejection of the target heart cells.Conclusion and significanceThe T. cruzi mitochondrion kinetoplast minicircle sequences transfer driven pathogenesis of Chagas disease is an ancient Cross-Kingdom DNA phenomenon of evolution and, therefore, paradigm research with effective purposing inhibitors is needed.Authors summaryChagas disease is considered the main cause of human heart failure in the Western Hemisphere. The treatment of the clinically manifested Chagas heart disease is considered unsatisfactory. Perhaps the most important problem in the field of Chagas disease is determination of the pathogenesis of the target heart cells lysis. We showed the transfer of the T. cruzi kDNA minicircle sequences into the genome of rabbits and mice, and to Bird refractory to the infections. The inoculation of a few T. cruzi in the fertile chicken eggs renders the kDNA sequences integration in the stem cells. Interestingly, the chicks that hatched retain the kDNA and develop the Chagas-like cardiomyopathy indistinguishable to that in the rabbits and mice. This result prompted the multidrug treatment of the Chagas heart disease with inhibitors of the eukaryotic cells division. We showed that nine out of 12 inhibitors prevented the transfer of the kDNA mutations into the macrophage genome, and that the treatment of the acutely T. cruzi-infected mice with Benznidazole + Ofloxacin + Azidothymidine lowered circa 2.5-fold the rate of the mutations in the chromosomes. These findings translated to the pathology showing inhibition of the heart lesions in the treated T. cruzi-infected mice. We suggest purposing new inhibitors should be tested to overturning the Chagas heart disease.

show abstract

“…пар нуклеотидов (п.н.)] и способны к ретротранспозициям [18]. К элементам SINE относятся Alu, длина которых 300 п.н., занимающие 11% всего генома человека и представленные более чем 1 млн копий.…”

Section: Introductionunclassified

Influence of retroelements on oncogenes and tumor suppressors in carcinogenesis: A review

Мустафин

2021

J. Mod. Onco.

View full text Add to dashboard Cite

Analysis of scientific literature data has revealed several ways in which retrotransposons, when activated, are involved in carcinogenesis. First, retroelements can encode oncogenic proteins. For example, the Np9 protein is translated from HERV-K endogenous retrovirus transcript. Second, retroelements are used as alternative promoters of protooncogenes. Accordingly, their activation contributes to the enhanced expression of oncogenes (e.g. CSF1R, IRF5, MET, RAB3IP, CHRM3). Third, retroelements are located in the introns of some genes, and upon their activation, they form chimeric transcripts, such as LTR2-FABP7, LTR-ALK, LTR-ERBB4, LINE1-MET, which have pronounced oncogenic activity. Fourth, retroelements are transposed into tumor suppressor genes (e.g. APC, NF1, MSH2, PTEN, RB1, TSC2, STK11, VHL) and inactivate them, which is associated with the presence of hot spots of insertional mutagenesis in them. As a result, the growth of tumors and the survival of their cells are stimulated. It is important to note that protein products of tumor suppressor genes, such as TP53, RB1, VHL, BRCA1, ATM, are characterized by the ability to inhibit the activity of retroelements. Accordingly, when even one oncosuppressive gene is inactivated, a kind of "vicious circle" can be triggered when the control of expression of retroelements is weakened. The latter, in turn, inactivate other tumor suppressors containing hot spots of insertional mutagenesis. This stimulates new pathways of carcinogenesis and the production of oncogenes associated with transposons. Thus, it is possible to explain in a new way the mechanisms of tumor formation in hereditary tumor syndromes. This is due to the fact that the weakening of the function of an oncosuppressor in a germinal heterozygous mutation may be sufficient to trigger a vicious circle involving retroelements, oncogenes and other oncosuppressors. Similar mechanisms are likely for sporadic malignant tumors. However, the initiating event in them can be the direct activation of transposons under the influence of stressors, chemical and physical carcinogens. In addition to the events described, activation of retroelements causes genomic instability, which contributes to complex genomic rearrangements often observed in malignant tumors. MicroRNAs and long noncoding RNAs, the sources of which are retroelements, also play an important role in the evolution of tumors. Their study is promising for the development of targeted therapy for neoplasms.

show abstract

Long Interspersed Nuclear Elements 1 (LINE1): The chimeric transcript L1-MET and its involvement in cancer

Cited by 9 publications

References 108 publications

The Potential of U6 and Its Copies in the Regulation of the Human Genome

The Potential of U6 and Its Copies in the Regulation of the Human Genome

The Trypanosoma cruzi kinetoplast DNA minicircle sequences transfer biomarker of the multidrug treatment of Chagas disease

Influence of retroelements on oncogenes and tumor suppressors in carcinogenesis: A review

Contact Info

Product

Resources

About