Autonomous transposons tune their sequences to ensure somatic suppression.

Transposable elements (TEs) are a major constituent of human genes, occupying approximately half of the intronic space. During pre-messenger RNA synthesis, intronic TEs are transcribed along with their host genes but rarely contribute to the final mRNA product because they are spliced out together with the intron and rapidly degraded. Paradoxically, TEs are an abundant source of RNA-processing signals through which they can create new introns, and also functional or non-functional chimeric transcripts.

Cerebral perfusion in type 2 diabetes mellitus: A preliminary study with MR perfusion.

Background: Type 2 diabetes mellitus (T2DM) is associated with altered cerebral vasoreactivity, cognitive impairment, and functional decline. Magnetic Resonance (MR) perfusion can be used to assess cerebral blood flow (CBF). The aim of this study is to analyze the association between diabetes mellitus and cerebral perfusion.

Dynamic antagonism between key repressive pathways maintains the placental epigenome.

DNA and Histone 3 Lysine 27 methylation typically function as repressive modifications and operate within distinct genomic compartments. In mammals, the majority of the genome is kept in a DNA methylated state, whereas the Polycomb repressive complexes regulate the unmethylated CpG-rich promoters of developmental genes. In contrast to this general framework, the extra-embryonic lineages display non-canonical, globally intermediate DNA methylation levels, including disruption of local Polycomb domains.

A multi-factor trafficking site on the spliceosome remodeling enzyme BRR2 recruits C9ORF78 to regulate alternative splicing.

The intrinsically unstructured C9ORF78 protein was detected in spliceosomes but its role in splicing is presently unclear. We find that C9ORF78 tightly interacts with the spliceosome remodeling factor, BRR2, in vitro. Affinity purification/mass spectrometry and RNA UV-crosslinking analyses identify additional C9ORF78 interactors in spliceosomes.

The intrinsically disordered TSSC4 protein acts as a helicase inhibitor, placeholder and multi-interaction coordinator during snRNP assembly and recycling.

Biogenesis of spliceosomal small nuclear ribonucleoproteins (snRNPs) and their recycling after splicing require numerous assembly/recycling factors whose modes of action are often poorly understood. The intrinsically disordered TSSC4 protein has been identified as a nuclear-localized U5 snRNP and U4/U6-U5 tri-snRNP assembly/recycling factor, but how TSSC4's intrinsic disorder supports TSSC4 functions remains unknown. Using diverse interaction assays and cryogenic electron microscopy-based structural analysis, we show that TSSC4 employs four conserved, non-contiguous regions to bind the PRPF8 Jab1/MPN domain and the SNRNP200 helicase at functionally important sites.

Chemotherapy-induced transposable elements activate MDA5 to enhance haematopoietic regeneration.

Haematopoietic stem cells (HSCs) are normally quiescent, but have evolved mechanisms to respond to stress. Here, we evaluate haematopoietic regeneration induced by chemotherapy. We detect robust chromatin reorganization followed by increased transcription of transposable elements (TEs) during early recovery.

Nuclear speckles: dynamic hubs of gene expression regulation.

Complex, multistep biochemical reactions that routinely take place in our cells require high concentrations of enzymes, substrates, and other structural components to proceed efficiently and typically require chemical environments that can inhibit other reactions in their immediate vicinity. Eukaryotic cells solve these problems by restricting such reactions into diffusion-restricted compartments within the cell called organelles that can be separated from their environment by a lipid membrane, or into membrane-less compartments that form through liquid-liquid phase separation (LLPS). One of the most easily noticeable and the earliest discovered organelle is the nucleus, which harbors the genetic material in cells where transcription by RNA polymerases produces most of the messenger RNAs and a plethora of noncoding RNAs, which in turn are required for translation of mRNAs in the cytoplasm.

SON and SRRM2 are essential for nuclear speckle formation.

Nuclear speckles (NS) are among the most prominent biomolecular condensates. Despite their prevalence, research on the function of NS is virtually restricted to colocalization analyses, since an organizing core, without which NS cannot form, remains unidentified. The monoclonal antibody SC35, raised against a spliceosomal extract, is frequently used to mark NS.

Nephronophthisis gene products display RNA-binding properties and are recruited to stress granules.

Mutations of cilia-associated molecules cause multiple developmental defects that are collectively termed ciliopathies. However, several ciliary proteins, involved in gating access to the cilium, also assume localizations at other cellular sites including the nucleus, where they participate in DNA damage responses to maintain tissue integrity. Molecular insight into how these molecules execute such diverse functions remains limited.

FLASH: ultra-fast protocol to identify RNA-protein interactions in cells.

Determination of the in vivo binding sites of RNA-binding proteins (RBPs) is paramount to understanding their function and how they affect different aspects of gene regulation. With hundreds of RNA-binding proteins identified in human cells, a flexible, high-resolution, high-throughput, highly multiplexible and radioactivity-free method to determine their binding sites has not been described to date. Here we report FLASH (Fast Ligation of RNA after some sort of Affinity Purification for High-throughput Sequencing), which uses a special adapter design and an optimized protocol to determine protein-RNA interactions in living cells.

Use of ARFI elastography in the prediction of placental invasion anomaly via a new Virtual Touch Quantification Technique.

We aimed to evaluate the efficiency of placental elasticity in predicting a placental invasion anomaly with the Virtual Touch Quantification (VTQ) technique. Pregnant women in the third trimester with suspected placental invasion anomaly were enrolled into the research (n = 58). The placenta was evaluated and divided into three equal parts as foetal edge (inner 1/3 of placenta), maternal edge (outer 1/3 of placenta) and the central part (central 1/3 of placenta).

Shear-wave elastography - virtual touch tissue quantification of fetal placentas with a single umbilical artery.

Objective: In this study, we aimed to evaluate the elasticities of fetal placentas with a single umbilical artery using the Virtual Touch Tissue Quantification (VTTQ) technique.

Materials And Methods: Pregnant women with fetuses with a single umbilical artery (SUA) and pregnant women with fetuses having three vessel cord (3VC) at 18-22 weeks of gestation were enrolled in the research. The placentas were evaluated and divided into three equal parts as the inner 1/3 of the placenta (fetal edge), the outer 1/3 of the placenta (maternal edge) and the central 1/3 of the placenta (central part).

A mutually exclusive stem-loop arrangement in roX2 RNA is essential for X-chromosome regulation in .

The X chromosome provides an ideal model system to study the contribution of RNA-protein interactions in epigenetic regulation. In male flies, roX long noncoding RNAs (lncRNAs) harbor several redundant domains to interact with the ubiquitin ligase male-specific lethal 2 (MSL2) and the RNA helicase Maleless (MLE) for X-chromosomal regulation. However, how these interactions provide the mechanics of spreading remains unknown.

Rapid evolutionary turnover underlies conserved lncRNA-genome interactions.

Many long noncoding RNAs (lncRNAs) can regulate chromatin states, but the evolutionary origin and dynamics driving lncRNA-genome interactions are unclear. We adapted an integrative strategy that identifies lncRNA orthologs in different species despite limited sequence similarity, which is applicable to mammalian and insect lncRNAs. Analysis of the roX lncRNAs, which are essential for dosage compensation of the single X chromosome in Drosophila males, revealed 47 new roX orthologs in diverse Drosophilid species across ∼40 million years of evolution.

Revealing long noncoding RNA architecture and functions using domain-specific chromatin isolation by RNA purification.

Little is known about the functional domain architecture of long noncoding RNAs (lncRNAs) because of a relative paucity of suitable methods to analyze RNA function at a domain level. Here we describe domain-specific chromatin isolation by RNA purification (dChIRP), a scalable technique to dissect pairwise RNA-RNA, RNA-protein and RNA-chromatin interactions at the level of individual RNA domains in living cells. dChIRP of roX1, a lncRNA essential for Drosophila melanogaster X-chromosome dosage compensation, reveals a 'three-fingered hand' ribonucleoprotein topology.

Tandem stem-loops in roX RNAs act together to mediate X chromosome dosage compensation in Drosophila.

Dosage compensation in Drosophila is an epigenetic phenomenon utilizing proteins and long noncoding RNAs (lncRNAs) for transcriptional upregulation of the male X chromosome. Here, by using UV crosslinking followed by deep sequencing, we show that two enzymes in the Male-Specific Lethal complex, MLE RNA helicase and MSL2 ubiquitin ligase, bind evolutionarily conserved domains containing tandem stem-loops in roX1 and roX2 RNAs in vivo. These domains constitute the minimal RNA unit present in multiple copies in diverse arrangements for nucleation of the MSL complex.

The MOF chromobarrel domain controls genome-wide H4K16 acetylation and spreading of the MSL complex.

The histone H4 lysine 16 (H4K16)-specific acetyltransferase MOF is part of two distinct complexes involved in X chromosome dosage compensation and autosomal transcription regulation. Here we show that the MOF chromobarrel domain is essential for H4K16 acetylation throughout the Drosophila genome and is required for spreading of the male-specific lethal (MSL) complex on the X chromosome. The MOF chromobarrel domain directly interacts with nucleic acids and potentiates MOF's enzymatic activity after chromatin binding, making it a unique example of a chromo-like domain directly controlling acetylation activity in vivo.

roX RNAs: non-coding regulators of the male X chromosome in flies.

The roX RNAs represent one of the paradigm examples of large non-coding RNAs involved in chromatin regulation. Interestingly, roX genes have a dual life. The RNA product is part of the MSL complex required for dosage compensation of the male X chromosome in Drosophila while the genomic location is used as a binding platform for MSL complex assembly.