Dynamic co-evolution of transposable elements and the piRNA pathway in African cichlid fishes.

Background: East African cichlid fishes have diversified in an explosive fashion, but the (epi)genetic basis of the phenotypic diversity of these fishes remains largely unknown. Although transposable elements (TEs) have been associated with phenotypic variation in cichlids, little is known about their transcriptional activity and epigenetic silencing. We set out to bridge this gap and to understand the interactions between TEs and their cichlid hosts.

U6 snRNA m6A modification is required for accurate and efficient splicing of C. elegans and human pre-mRNAs.

pre-mRNA splicing is a critical feature of eukaryotic gene expression. Both cis- and trans-splicing rely on accurately recognising splice site sequences by spliceosomal U snRNAs and associated proteins. Spliceosomal snRNAs carry multiple RNA modifications with the potential to affect different stages of pre-mRNA splicing.

Dynamic co-evolution of transposable elements and the piRNA pathway in African cichlid fishes.

East African cichlid fishes have diversified in an explosive fashion, but the (epi)genetic basis of the phenotypic diversity of these fishes remains largely unknown. Although transposable elements (TEs) have been associated with phenotypic variation in cichlids, little is known about their transcriptional activity and epigenetic silencing. Here, we describe dynamic patterns of TE expression in African cichlid gonads and during early development.

rnaCrosslinkOO: an object-oriented R package for the analysis of RNA structural data generated by RNA crosslinking experiments.

Summary: RNA (ribonucleic acid) molecules have secondary and tertiary structures in vivo which play a crucial role in cellular processes such as the regulation of gene expression, RNA processing and localization. The ability to investigate these structures will enhance our understanding of their function and contribute to the diagnosis and treatment of diseases caused by RNA dysregulation. However, there are no mature pipelines or packages for processing and analyzing complex in vivo RNA structural data.

The histone chaperone SPT2 regulates chromatin structure and function in Metazoa.

Histone chaperones control nucleosome density and chromatin structure. In yeast, the H3-H4 chaperone Spt2 controls histone deposition at active genes but its roles in metazoan chromatin structure and organismal physiology are not known. Here we identify the Caenorhabditis elegans ortholog of SPT2 (CeSPT-2) and show that its ability to bind histones H3-H4 is important for germline development and transgenerational epigenetic gene silencing, and that spt-2 null mutants display signatures of a global stress response.

Canalisation and plasticity on the developmental manifold of Caenorhabditis elegans.

How do the same mechanisms that faithfully regenerate complex developmental programmes in spite of environmental and genetic perturbations also allow responsiveness to environmental signals, adaptation and genetic evolution? Using the nematode Caenorhabditis elegans as a model, we explore the phenotypic space of growth and development in various genetic and environmental contexts. Our data are growth curves and developmental parameters obtained by automated microscopy. Using these, we show that among the traits that make up the developmental space, correlations within a particular context are predictive of correlations among different contexts.

U6 snRNA m6A modification is required for accurate and efficient cis- and trans-splicing of mRNAs.

pre-mRNA splicing is a critical feature of eukaryotic gene expression. Many eukaryotes use cis-splicing to remove intronic sequences from pre-mRNAs. In addition to cis-splicing, many organisms use trans-splicing to replace the 5' ends of mRNAs with a non-coding spliced-leader RNA.

Identification of putative reader proteins of 5-methylcytosine and its derivatives in RNA.

Methylation of carbon-5 of cytosines (m C) is a conserved post-transcriptional nucleotide modification of RNA with widespread distribution across organisms. It can be further modified to yield 5-hydroxymethylcytidine (hm C), 5-formylcytidine (f C), 2´-O-methyl-5-hydroxymethylcytidine (hm Cm) and 2´-O-methyl-5-formylcytidine (f Cm). How m C, and specially its derivates, contribute to biology mechanistically is poorly understood.

A highly contiguous genome assembly reveals sources of genomic novelty in the symbiotic fungus Rhizophagus irregularis.

The root systems of most plant species are aided by the soil-foraging capacities of symbiotic arbuscular mycorrhizal (AM) fungi of the Glomeromycotina subphylum. Despite recent advances in our knowledge of the ecology and molecular biology of this mutualistic symbiosis, our understanding of the AM fungi genome biology is just emerging. Presented here is a close to T2T genome assembly of the model AM fungus Rhizophagus irregularis DAOM197198, achieved through Nanopore long-read DNA sequencing and Hi-C data.

Loss of the E3 ubiquitin ligases UBR-5 or HECD-1 restores development in the absence of SWI/SNF function.

SWItch/sucrose non-fermenting (SWI/SNF) complexes are a family of chromatin remodelers that are conserved across eukaryotes. Mutations in subunits of SWI/SNF cause a multitude of different developmental disorders in humans, most of which have no current treatment options. Here, we identify an alanine-to-valine-causing mutation in the SWI/SNF subunit ( in humans) that prevents embryonic lethality in nematodes harboring a loss-of-function mutation in the SWI/SNF subunit ( in humans).

Epigenetic inheritance of gene silencing is maintained by a self-tuning mechanism based on resource competition.

Biological systems can maintain memories over long timescales, with examples including memories in the brain and immune system. It is unknown how functional properties of memory systems, such as memory persistence, can be established by biological circuits. To address this question, we focus on transgenerational epigenetic inheritance in Caenorhabditis elegans.

Mouse primordial germ-cell-like cells lack piRNAs.

PIWI-interacting RNAs (piRNAs) are small RNAs bound by PIWI-clade Argonaute proteins that function to silence transposable elements (TEs). Following mouse primordial germ cell (mPGC) specification around E6.25, fetal piRNAs emerge in male gonocytes from E13.

ER-associated RNA silencing promotes ER quality control.

The endoplasmic reticulum (ER) coordinates mRNA translation and processing of secreted and endomembrane proteins. ER-associated degradation (ERAD) prevents the accumulation of misfolded proteins in the ER, but the physiological regulation of this process remains poorly characterized. Here, in a genetic screen using an ERAD model substrate in Caenorhabditis elegans, we identified an anti-viral RNA interference pathway, referred to as ER-associated RNA silencing (ERAS), which acts together with ERAD to preserve ER homeostasis and function.

targeting using CRISPR/Cas9 in the Malawi cichlid .

Identifying genetic loci underlying trait variation provides insights into the mechanisms of diversification, but demonstrating causality and characterizing the role of genetic loci requires testing candidate gene function, often in non-model species. Here we establish CRISPR/Cas9 editing in , a generalist cichlid of the remarkably diverse Lake Malawi radiation. By targeting the gene required for melanin synthesis in other vertebrate species, we show efficient editing and germline transmission.

Alternative splicing modulation by G-quadruplexes.

Alternative splicing is central to metazoan gene regulation, but the regulatory mechanisms are incompletely understood. Here, we show that G-quadruplex (G4) motifs are enriched ~3-fold near splice junctions. The importance of G4s in RNA is emphasised by a higher enrichment for the non-template strand.

Taming transposable elements in vertebrates: from epigenetic silencing to domestication.

Transposable element (TE)-derived sequences are ubiquitous in most eukaryotic genomes known to date. Because their expression and mobility can lead to genomic instability, several pathways have evolved to control TEs. Nevertheless, TEs represent an important source of genomic novelty and are often co-opted for novel functions that are relevant for phenotypic divergence and adaptation.

TransposonUltimate: software for transposon classification, annotation and detection.

Most genomes harbor a large number of transposons, and they play an important role in evolution and gene regulation. They are also of interest to clinicians as they are involved in several diseases, including cancer and neurodegeneration. Although several methods for transposon identification are available, they are often highly specialised towards specific tasks or classes of transposons, and they lack common standards such as a unified taxonomy scheme and output file format.

Receptor tyrosine kinases regulate signal transduction through a liquid-liquid phase separated state.

The recruitment of signaling proteins into activated receptor tyrosine kinases (RTKs) to produce rapid, high-fidelity downstream response is exposed to the ambiguity of random diffusion to the target site. Liquid-liquid phase separation (LLPS) overcomes this by providing elevated, localized concentrations of the required proteins while impeding competitor ligands. Here, we show a subset of phosphorylation-dependent RTK-mediated LLPS states.

RNA uridyl transferases TUT4/7 differentially regulate miRNA variants depending on the cancer cell type.

The human terminal uridyl transferases TUT4 and TUT7 (TUT4/7) catalyze the additions of uridines at the 3' end of RNAs, including the precursors of the tumor suppressor miRNA let-7 upon recruitment by the oncoprotein LIN28A. As a consequence, let-7 family miRNAs are down-regulated. Disruption of this TUT4/7 activity inhibits tumorigenesis.