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Here, the authors find that BMAL1, best known for controlling the body clock, partners with TRIM28 in naïve pluripotent stem cells to repress retrotransposons.

Giant transposons, known as ‘Starships’, mediate horizontal gene transfer between fungal genomes. Here, Sato et al. show that Starships occupy genome regions crucial for infection in a plant pathogenic fungus, show signatures of horizontal transfer between distant fungal species, and may facilitate the formation of new virulence genes.

Gene duplication often leads to paralogs with distinct functions. Here, the authors show that two paralogous proteins NRBP1 and NRBP2 oppositely regulate L1 retrotransposition by modulating L1 mRNA and ORF1p association, with NRBP2 promoting NRBP1 degradation via heterodimerization.

Here, the authors develop a high-throughput assay to measure the jumping potential of thousands of transposons in parallel.

A study of retrotransposon activity repurposes a retroelement called R2Tocc to create a programmable system called STITCHR that enables diverse genome edits including efficient, scarless large payload insertions.

A pangenome of the Cannabis genus including 193 genomes demonstrates high variability in most of the genome but low diversity in cannabinoid synthesis genes and provides a resource for future genetic studies and crop optimization.

H-NS is a DNA-binding protein that silences transcription of horizontally acquired genes in bacteria. Here, Cooper et al. show that, in addition, H-NS acts as a transposon capture protein, driving transposon insertion into silenced genes and away from transcribed and essential genes.

Here, the authors show that an inverted-repeat transposon located next to the pattern recognition receptor ELONGATION FACTOR-TU RECEPTOR (EFR)-encoding gene in Arabidopsis controls chromatin organization, EFR gene expression and plant immune response.

piggyBat is the only known DNA transposon active in mammals. Here the authors used cellular assays and 3D structure to show that sequences within the transposon ends restrict activity, and also how transposition activity can be substantially increased.

An Arabidopsis long terminal repeat retrotransposon integrates de novo into regions occupied by centromere-specific histone variant, showing the impact of centromeric chromatin on transposable element-mediated rapid centromere evolution, with relevance across eukaryotic genomes.

The assembly of diverse immunoglobulin genes results in part from Rag protein–mediated DNA double-strand breaks at the edges of immunoglobulin gene segments, followed by the combinatorial reassembly of these segments. A transposase from the insect Helicoverpa zea is now shown to be active in vitro, and its breakage and joining activities resemble those of Rag, suggesting a common progenitor.

InducTn-seq, a method for inducible mutagenesis followed by transposon insertion site sequencing, enables temporal control of transposition to bypass population bottlenecks and enable the quantification of gene fitness during in vivo Citrobacter rodentium infection.

RNA-guided CRISPR-associated transposases (CAST) are natural systems with broad potential in biotechnology. Here, the authors report compact type V-K CAST discovered from genome-resolved metagenomics and demonstrate targeted integration of a large transgene to a safe-harbor site in the human genome.

Here, the authors show that CRISPR-associated transposons can co-opt other CRISPR arrays found in the same cell. Such interactions must be considered when porting these systems into new hosts.

Here, Zhao et al. use cryo-EM to show how MuB forms helical filaments around DNA. These structures play a crucial role in target DNA selection and transposition, shedding light on MuB’s functional mechanism.

Using cryo-electron microscopy, the structural mechanism by which non-coding bridge RNA confers target and donor DNA specificity to IS110 recombinases for programmable DNA recombination is explored.

A bispecific non-coding RNA expressed by the IS110 family of mobile genetic elements forms the basis of a programmable genome-editing system that enables the insertion, excision or inversion of specific target DNA sequences.

Bacterial heteroresistance is a medically relevant phenotype where small antibiotic-resistant subpopulations coexist within predominantly susceptible bacterial populations. Here, Nicoloff et al. describe how three different mechanisms that increase the copy number of resistance genes can lead to unstable and transient heteroresistance.

SAFB proteins protect genome integrity by preventing retrotransposition of L1 elements yet maintaining splicing integrity, via prevention of the exonization of previously integrated transposable elements, a major constituent of human genes.

Mutations in condensin subunits cause microcephaly, but the underlying molecular mechanisms remain elusive. Here, the authors show that unrestricted retrotransposable element activity impairs brain development in condensin insufficient organisms.

Guillaume Bourque and colleagues report genome-wide binding profiles of the OCT4, NANOG and CTCF proteins in human ES cells as determined by ChIP-sequencing. They find that the binding profiles of OCT4 and NANOG are different in human and mouse ES cells, and some of the differences in bound sites are due to transposable elements.

The ability of retrotransposons to mobilize and insert into genes presents a challenge to a cell needing to maintain its genomic integrity. These authors have studied retrotransposition in embryonic carcinoma-derived cells. On insertion into DNA, the retrotransposon is quickly silenced, but the retrotransposon-specificity of this process implies that multiple silencing mechanisms may exist. Once cells differentiate, the ability to silence newly introduced retrotransposons is lost but previously inactivated retrotransposons remain inactive.

The transcription of repetitive elements such as retrotransposons is normally repressed, to prevent their unchecked dissemination throughout the genome. This study shows that heat stress induces the transcription of the ONSEN retroelement. The accumulation of ONSEN is suppressed by small interfering RNAs. When siRNAs were absent, new ONSEN insertions were found in the progeny of heat-stressed plants, having transposed during differentiation. These results imply a memory of stress that can be counteracted by siRNAs.

Epigenetic control of extrachromosomal circular DNA (eccDNA) compartment and the relationships between eccDNA and plant genome stability remain unclear. Here, the authors investigate eccDNA and structural variations in Arabidopsis epigenetic mutants to reveal the eccDNA repertoire and its impact on genome stability.

Zhen and colleagues show that nuclear cGAS represses L1 retrotransposition to stabilize the genome by enhancing the interaction between ORF2p and the E3 ligase TRIM41 upon DNA damage, which leads to the ubiquitination and degradation of ORF2p.

Human LINE-1 ORF2p relies on upstream single-stranded target DNA to position the adjacent duplex in the endonuclease active site for nicking of the longer DNA strand, with a single nick generating a staggered DNA break.

PIWI-interacting RNAs (piRNAs) are regulatory RNAs that bind to PIWI proteins to control transposons and maintain genome integrity. Here the authors characterized their binding specificity and reveal the 5′ nucleotide bias of the Drosophila Piwi protein, through mutation of its specificity loop.

Human cytomegalovirus (HCMV) hijacks host L1 retrotransposon to supercharge its replication. This novel virus-transposon interaction reveals a strategy for viruses to exploit host machinery, accelerating viral DNA replication and enhancing fitness.

We find that massive genome expansion seems to be related to a reduction of PIWI-interacting RNAs and C2H2 zinc-finger and KRAB-domain protein genes that suppress transposable element expansion, and lungfish chromosomes still conservatively reflect the ur-tetrapod karyotype.

Spínola-Amilibia et al. present the cryo-EM structure of the IS21 transposase in complex with the donor DNA and show that IstA recognizes the transposon ends with a highly intertwined configuration to facilitate the strand-transfer reaction.

Cryo-electron microscopy analysis of the Deinococcus radiodurans ISDra2 TnpB in complex with its cognate ωRNA and target DNA provides insights into the mechanism of TnpB function and the evolution of CRISPR–Cas12 effectors.

Solution and cryogenic electron microscopy studies using IS21 as a model transposase system show how AAA+ ATPases induce structural changes to prime target DNA and activate their associated transposases.

Here the authors elucidate how epigenetic regulation influences the regulatory impact of transposable elements in the human genome using cellular models of the neurodegenerative disease XDP, which is caused by an SVA insertion at the TAF1 locus.

Fusion of rice Pong transposase to the Cas9 or Cas12a programmable nucleases provides sequence-specific targeted insertion of enhancer elements, an open reading frame and gene expression cassette into the genome of the model plant Arabidopsis and crop soybean.

Transgenes are inserted into human cells by 2-RNA delivery of a retroelement protein and template.

Endogenous retroviruses constitute 5–10% of mammalian genome space. This study characterize the bovine ERVK[2-1- LTR] clade showing that its activity varies between individuals as a function of the number of inherited autonomous elements, yet that most de novo insertions are non-autonomous elements lacking functional genes.

HIV-1 integration sites are biased towards actively transcribed genes, likely mediated by binding of the viral integrase (IN) protein to host factors. Here, Winans et al. show that the K258R point mutation in IN eredirects viral DNA integration to the centromeres of host chromosomes, which may affect HIV latency.

The RNA-directed nuclease TnpB from Deinococcus radiodurans can be reprogrammed to cleave DNA target sites in human cells.

Ty3 retrotransposon integrates with an exquisite specificity upstream of RNA Polymerase III-transcribed genes, such as transfer RNAs. Here the authors resolve a cryo-EM structure of an active Ty3 intasome in complex with a TFIIIB-bound tRNA promoter, shedding light into the molecular determinants of harmless retrotransposition.

The human silencing hub (HUSH) complex uses introns to distinguish intronless foreign DNA from intron-containing host DNA and modifies chromatin to silence transcription of retrotransposons and retroviruses.

Structural studies on Scytonema hofmanni CRISPR-associated transposon protein complexes indicate a mechanism for RNA-guided DNA transposition involving Cas12k, TnsC and TnsB.

Transposable elements in somatic cells become increasingly mobile during ageing. Here, the authors show that in the nematode Caenorhabditis elegans, downregulation of transposable elements extends lifespan, and that their increases with age are coupled with progressively growing N⁶-adenine methylation in these genetic loci.

X-ray crystallography, cryo-electron microscopy, structural modelling, biochemistry, cell biology, and evolutionary analysis enable characterization of ORF2p, the reverse transcriptase of the ancient ‘parasitic’ LINE-1 retrotransposon that has written around one-third of the human genome.

TnpB and IscB nucleases use transposon-encoded guide RNAs to target genomic sequences for cleavage, thereby favouring copying and spreading of transposable elements.

Here the authors show that, in the absence of Pi3K–AKT–mTOR signaling, AGO2 accumulates in the nucleus of quiescent cells, where it binds to young retrotransposons and represses their expression.