Retrotransposons as regulators of gene expression

Elbarbary, Reyad A.; Lucas, Bronwyn A; Maquat, Lynne E.

doi:10.1126/science.aac7247

Cited by 355 publications

(335 citation statements)

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“…The first ORF encodes an RNA-binding protein that functions as a chaperone and the second ORF encodes a protein complex that has endonuclease and reverse transcriptase activity. Mutsu retrotransposons belong to the group of long interspersed nuclear elements (LINE) that have a distinct way of replicating and integrating themselves into the genome (Swergold 1990;Ostertag and Kazazian 2001;Elbarbary et al 2016). Thus far, three subfamilies of Mutsu have been identified: MutsuDr1-3.…”

Section: Introductionmentioning

confidence: 99%

Linking maternal and somatic 5S rRNA types with different sequence-specific non-LTR retrotransposons

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5S rRNA is a ribosomal core component, transcribed from many gene copies organized in genomic repeats. Some eukaryotic species have two 5S rRNA types defined by their predominant expression in oogenesis or adult tissue. Our next-generation sequencing study on zebrafish egg, embryo, and adult tissue identified maternal-type 5S rRNA that is exclusively accumulated during oogenesis, replaced throughout the embryogenesis by a somatic-type, and thus virtually absent in adult somatic tissue. The maternal-type 5S rDNA contains several thousands of gene copies on chromosome 4 in tandem repeats with small intergenic regions, whereas the somatic-type is present in only 12 gene copies on chromosome 18 with large intergenic regions. The nine-nucleotide variation between the two 5S rRNA types likely affects TFIII binding and riboprotein L5 binding, probably leading to storage of maternal-type rRNA. Remarkably, these sequence differences are located exactly at the sequence-specific target site for genome integration by the 5S rRNA-specific Mutsu retrotransposon family. Thus, we could define maternal-and somatic-type MutsuDr subfamilies. Furthermore, we identified four additional maternal-type and two new somatic-type MutsuDr subfamilies, each with their own target sequence. This target-site specificity, frequently intact maternal-type retrotransposon elements, plus specific presence of Mutsu retrotransposon RNA and piRNA in egg and adult tissue, suggest an involvement of retrotransposons in achieving the differential copy number of the two types of 5S rDNA loci.

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Section: Introductionmentioning

confidence: 99%

Linking maternal and somatic 5S rRNA types with different sequence-specific non-LTR retrotransposons

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et al. 2016

RNA

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“…A genomic consequence of their mobilization is the induction of new mutations and chromosomal rearrangements that may have deleterious effects on fitness. However, they may also provide a fundamental contribution to genetic variation and evolutionary changes (Fedoroff 2012;Warren et al 2015;Elbarbary et al 2016;Mita and Boeke 2016). TE activation is suppressed by specific silencing mechanisms that act both at the transcriptional level, through chromatin modifications, and at the post-transcriptional level (Buchon and Vaury 2006).…”

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confidence: 99%

Production of Small Noncoding RNAs from the flamenco Locus Is Regulated by the gypsy Retrotransposon of Drosophila melanogaster

et al. 2016

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Protective mechanisms based on RNA silencing directed against the propagation of transposable elements are highly conserved in eukaryotes. The control of transposable elements is mediated by small noncoding RNAs, which derive from transposonrich heterochromatic regions that function as small RNA-generating loci. These clusters are transcribed and the precursor transcripts are processed to generate Piwi-interacting RNAs (piRNAs) and endogenous small interfering RNAs (endo-siRNAs), which silence transposable elements in gonads and somatic tissues. The flamenco locus is a Drosophila melanogaster small RNA cluster that controls gypsy and other transposable elements, and has played an important role in understanding how small noncoding RNAs repress transposable elements. In this study, we describe a cosuppression mechanism triggered by new euchromatic gypsy insertions in genetic backgrounds carrying flamenco alleles defective in gypsy suppression. We found that the silencing of gypsy is accompanied by the silencing of other transposons regulated by flamenco, and of specific flamenco sequences from which small RNAs against gypsy originate. This cosuppression mechanism seems to depend on a post-transcriptional regulation that involves both endo-siRNA and piRNA pathways and is associated with the occurrence of developmental defects. In conclusion, we propose that new gypsy euchromatic insertions trigger a post-transcriptional silencing of gypsy sense and antisense sequences, which modifies the flamenco activity. This cosuppression mechanism interferes with some developmental processes, presumably by influencing the expression of specific genes. KEYWORDS transposon; small RNA; RNA silencing; primary transcript; ecdysis E UKARYOTIC genomes consist in part of sequences derived from a wide variety of transposable elements (TEs), some of which can mobilize to new genomic locations (de Koning et al. 2011). A genomic consequence of their mobilization is the induction of new mutations and chromosomal rearrangements that may have deleterious effects on fitness. However, they may also provide a fundamental contribution to genetic variation and evolutionary changes (Fedoroff 2012;Warren et al. 2015;Elbarbary et al. 2016;Mita and Boeke 2016). TE activation is suppressed by specific silencing mechanisms that act both at the transcriptional level, through chromatin modifications, and at the post-transcriptional level (Buchon and Vaury 2006). Piwi-interacting RNAs (piRNAs), a distinct class of 24-to 30-nt-long RNAs produced by a Dicer-independent biogenesis pathway, are involved in the recognition and selective silencing of transposons during gametogenesis (Sarot et al. 2004;Kalmykova et al. 2005). In the Drosophila ovary germline, the coordinated action of aubergine (aub), Argonaute 3 (AGO3), and piwi suppresses activity of a broad group of TEs through the formation of piRNAs involving both a primary processing and a secondary "ping-pong" amplification loop (Brennecke et al. 2007;Gunawardane et al. 2007;Li et al. 2009;Malone...

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“…First, RNA editing and splicing, processes that may be coordinated in mammals [95] , can be affected by retrotransposons. More than 90% of A-to-I RNA editing sites in humans are found within Alu elements [96][97][98] . Considering that approximately 75% of all known human genes bear Alu sequences within their introns and/or untranslated regions (UTRs) [99] , edited intronic Alu elements may have an impact on the transcript metabolism [98] .…”

Section: R E T R O T R a N S P O S O N S : A W E B O F Sophisticated mentioning

confidence: 99%

“…More than 90% of A-to-I RNA editing sites in humans are found within Alu elements [96][97][98] . Considering that approximately 75% of all known human genes bear Alu sequences within their introns and/or untranslated regions (UTRs) [99] , edited intronic Alu elements may have an impact on the transcript metabolism [98] . Moreover, retrotransposons can influence splicing through exon skipping [100][101][102][103][104][105] , alternative donor or acceptor splice sites [106] , shift of splicing patterns from constitutive to alternative [107] , induction of intron retention and exonization [108][109][110][111] .…”

Section: R E T R O T R a N S P O S O N S : A W E B O F Sophisticated mentioning

confidence: 99%

On the Concept Of Retrotransposons: Controlling Genome and Making Stress Memories

Noutsopoulos

2016

Journal of Biochemistry and Molecular Biology Research

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Retrotransposons constitute discrete genetic entities that have attained a large fraction of mammalian genomes during evolution. Their inhabitance as well as their functional impact on host genome has definitively revised the initial viewpoint of "junk DNA". Nowadays, it is widely accepted that retrotransposons may control genome through a variety of mechanisms, affecting different cellular processes. Here, I survey their impact on genome architecture and function with an emphasis on their interwoven relationship with stress.

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Retrotransposons as regulators of gene expression

Cited by 355 publications

References 100 publications

Linking maternal and somatic 5S rRNA types with different sequence-specific non-LTR retrotransposons

Linking maternal and somatic 5S rRNA types with different sequence-specific non-LTR retrotransposons

Production of Small Noncoding RNAs from the flamenco Locus Is Regulated by the gypsy Retrotransposon of Drosophila melanogaster

On the Concept Of Retrotransposons: Controlling Genome and Making Stress Memories

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