The impact of retrotransposons on human genome evolution

Cordaux, Richard; Batzer, Mark A.

doi:10.1038/nrg2640

Cited by 1,450 publications

(1,452 citation statements)

References 166 publications

Supporting

Mentioning

1,421

Contrasting

Unclassified

Order By: Relevance

“…Nearly 45 % of the human genome contains transposon elements [12]. Piwi-interacting RNAs (piRNAs) are noncoding RNAs that inhibit transposon elements in germ cells as an endogenous defense system [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Association of MOV10L1 gene polymorphisms and male infertility in azoospermic men with complete maturation arrest

Sarkardeh

Totonchi

Asadpour

et al. 2014

J Assist Reprod Genet

View full text Add to dashboard Cite

Purpose The present research was undertaken to study probable genetic variations of MOV10L1 in 30 infertile men that had complete maturation arrest in their spermatocyte levels and 70 fertile men as the control group. Methods We performed polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) on extracted DNAs and sequencing was used to confirm the results.Identified polymorphisms in the MOV10L1 were further subjected to a haplotype analysis. Results We identified eight single nucleotide polymorphisms (SNPs): one missense (rs2272837) and four nonsense polymorphisms (rs2272836, rs11704548, rs2272838, rs138271) in the exonic sequences and three polymorphisms (rs12170772, rs2272840, rs17248147) in the intronic regions. With the exception of rs2272838, there was a statistically significant association in all polymorphisms between study population (P<0.05). The result of haplotyping analysis showed ten possible haplotypes, from which five were significantly increased in infertile patients compared with the control group. Conclusions Our results suggest that MOV10L1 gene polymorphisms in the studied infertile males with complete maturation arrest are linked to infertility.

show abstract

Section: Introductionmentioning

confidence: 99%

Association of MOV10L1 gene polymorphisms and male infertility in azoospermic men with complete maturation arrest

Sarkardeh

Totonchi

Asadpour

et al. 2014

J Assist Reprod Genet

View full text Add to dashboard Cite

show abstract

“…L1 mobilizes replicatively from one location in the genome to another by a 'copy-and-paste' mechanism, and it has been proposed to be a remnant of an ancient retrovirus 12,16 . Active and inactive L1s have been implicated in the evolution of mammalian genomes and are linked to cell-based diseases, including cancer [17][18][19] . In addition, somatic L1 insertions are biased toward regions of cancer-specific DNA hypomethylation, thus suggesting that L1 insertions may provide a selective advantage during tumorigenesis 20 .…”

mentioning

confidence: 99%

miR-128 represses L1 retrotransposition by binding directly to L1 RNA

Hamdorf

Idica

Zisoulis

et al. 2015

Nat Struct Mol Biol

View full text Add to dashboard Cite

VOLUME 22 NUMBER 10 OCTOBER 2015 nature structural & molecular biology a r t i c l e s microRNAs (miRs) are a class of small (~22-nt) genomically encoded molecules that inhibit translational initiation and stimulate decay of mRNA targets 1,2 . miRs are transcribed by RNA polymerase II and processed by the RNase III enzymes-Dicer and Drosha with its binding partner, DGCR8-to produce short double-stranded RNAs in the nucleus. One strand associates with the Argonaute (Ago) protein, thus forming the miR-mediated silencing complex (miRISC). miRs guide the pairing of miRISC, with imperfect complementarity, to sequences in target mRNAs, thus resulting in their subsequent destabilization and translational repression of the target 3 . The 'seed sequence' , at nucleotides 2-8, is a key determinant for miRISC-target recognition 4,5 . Recent data have shown that 35-40% of miR-binding sites are found in 3′ untranslated regions (UTRs), 40-50% in coding regions and <5% in 5′-UTR regions of mRNAs 6,7 . More than 60% of the human transcriptome has been predicted to be under miR regulation, thus making this post-transcriptional control pathway as important as protein pathways in the regulation of cell functions 2 . It is clear that miRs have essential roles in regulating diverse functions in normal and diseased cells 8,9 .L1 belongs to the most abundant class of autonomous transposable elements 10 . Human L1 contains two open reading frames, ORF1 and ORF2, which encode a protein with RNA-binding and nucleotide acid-chaperone activity (ORF1) 11 and a protein with endonuclease and reverse-transcriptase activities (ORF2) 12-15 , respectively. L1 mobilizes replicatively from one location in the genome to another by a 'copy-and-paste' mechanism, and it has been proposed to be a remnant of an ancient retrovirus 12,16 . Active and inactive L1s have been implicated in the evolution of mammalian genomes and are linked to cell-based diseases, including cancer [17][18][19] . In addition, somatic L1 insertions are biased toward regions of cancer-specific DNA hypomethylation, thus suggesting that L1 insertions may provide a selective advantage during tumorigenesis 20 . Mechanisms that operate at different levels in gene-expression hierarchies have been selected to control transposition-mediated mutagenesis and mitigate the potential negative effects of newly inserted elements. In germ cells, a specific small-RNA subtype (piwi-interacting RNAs (piRNAs)) efficiently counteracts L1 activity, but these RNAs are not expressed in nongerm cells 21,22 . Somatic cells attenuate element mobilization by DNA methylation of the L1 promoter 23 . Other methods of regulation are mediated by APOBEC proteins 24,25 , microprocessor interactions 26 and Ago-mediated RNA interference in mouse embryonic stem cells 27 . L1-promoter silencing is greatly attenuated, and L1 transcription is reactivated in hypomethylated cells, such as cancer cells and tumor-initiating cells, and is also reactivated during reprogramming [28][29][30] . Because miRs act as regulators of g...

show abstract

“…5,6 Despite their relatively short size and sequence divergence, non-allelic Alu/Alu recombination events have contributed to a great deal of genomic instability, including evolution of the human genome. 7 and extensive DNA rearrangements associated with human disease. 8,9 It is estimated that about 0.3% of new human genetic diseases are caused by homeologous Alu/Alu recombination and it is likely that they also represent an important form of somatic instability, particularly in tumors.…”

Section: Introductionmentioning

confidence: 99%