Exosomal miRNAs from Prostate Cancer Impair Osteoblast Function in Mice.

Prostate cancer (PCa) is the most frequent malignancy in older men with a high propensity for bone metastases. Characteristically, PCa causes osteosclerotic lesions as a result of disrupted bone remodeling. Extracellular vesicles (EVs) participate in PCa progression by conditioning the pre-metastatic niche.

The RNA binding protein human antigen R is a gatekeeper of liver homeostasis.

Background And Aims: NAFLD is initiated by steatosis and can progress through fibrosis and cirrhosis to HCC. The RNA binding protein human antigen R (HuR) controls RNAs at the posttranscriptional level; hepatocyte HuR has been implicated in the regulation of diet-induced hepatic steatosis. The present study aimed to understand the role of hepatocyte HuR in NAFLD development and progression to fibrosis and HCC.

Intrinsically disordered protein PID-2 modulates Z granules and is required for heritable piRNA-induced silencing in the Caenorhabditis elegans embryo.

In Caenorhabditis elegans, the piRNA (21U RNA) pathway is required to establish proper gene regulation and an immortal germline. To achieve this, PRG-1-bound 21U RNAs trigger silencing mechanisms mediated by RNA-dependent RNA polymerase (RdRP)-synthetized 22G RNAs. This silencing can become PRG-1-independent and heritable over many generations, a state termed RNA-induced epigenetic gene silencing (RNAe).

Innate Immune Training of Granulopoiesis Promotes Anti-tumor Activity.

Trained innate immunity, induced via modulation of mature myeloid cells or their bone marrow progenitors, mediates sustained increased responsiveness to secondary challenges. Here, we investigated whether anti-tumor immunity can be enhanced through induction of trained immunity. Pre-treatment of mice with β-glucan, a fungal-derived prototypical agonist of trained immunity, resulted in diminished tumor growth.

PETISCO is a novel protein complex required for 21U RNA biogenesis and embryonic viability.

Piwi proteins are important for germ cell development in most animals. These proteins are guided to specific targets by small guide RNAs, referred to as piRNAs or 21U RNAs in In this organism, even though genetic screens have uncovered 21U RNA biogenesis factors, little is known about how these factors interact or what they do. Based on the previously identified 21U biogenesis factor PID-1 (piRNA-induced silencing-defective 1), we here define a novel protein complex, PETISCO (PID-3, ERH-2, TOFU-6, and IFE-3 small RNA complex), that is required for 21U RNA biogenesis.

RppH can faithfully replace TAP to allow cloning of 5'-triphosphate carrying small RNAs.

RNA interference was first described in the nematode . Ever since, several new endogenous small RNA pathways have been described and characterized to different degrees. The very prominent secondary small interfering RNAs, also called 22G-RNAs, bear a 5' triphosphate group after loading into an Argonaute protein.

Maternal and zygotic gene regulatory effects of endogenous RNAi pathways.

Endogenous small RNAs (sRNAs) and Argonaute proteins are ubiquitous regulators of gene expression in germline and somatic tissues. sRNA-Argonaute complexes are often expressed in gametes and are consequently inherited by the next generation upon fertilization. In Caenorhabditis elegans, 26G-RNAs are primary endogenous sRNAs that trigger the expression of downstream secondary sRNAs.

Identification of Tox chromatin binding properties and downstream targets by DamID-Seq.

In recent years, DNA adenine methyltransferase identification (DamID) has emerged as a powerful tool to profile protein-DNA interaction on a genome-wide scale. While DamID has been primarily combined with microarray analyses, which limits the spatial resolution and full potential of this technique, our group was the first to combine DamID with sequencing (DamID-Seq) for characterizing the binding loci and properties of a transcription factor (Tox) (sequencing data available at NCBI's Gene Expression Omnibus under the accession number GSE64240). Our approach was based on the combination and optimization of several bioinformatics tools that are here described in detail.

White matter synapses: form, function, and dysfunction.

Synaptic transmission in the CNS represents the classic mechanism through which neural cells communicate. While vesicular neurotransmitter release has been known to be the preserve of gray matter, it is now known that synaptic-style release of glutamate, the brain's major excitatory neurotransmitter, occurs deep in white matter. Here it permits communication between axons and glial cells, enabling axon activity to couple with high fidelity to glial physiology.

Glia as transmitter sources and sensors in health and disease.

Glial cells express a bewildering array of neurotransmitter receptors. To illustrate the complexity of expression, we have assayed non-glutamatergic neurotransmitter receptor mRNA in isolated rat optic nerve, a preparation devoid of neurons and neuronal synapses and from which relatively pure "glial" RNA can be isolated. Of the 44 receptor subunits examined which span the GABA-A, nicotinic, adreno- and glycine receptor families, over three quarters were robustly expressed in this mixed population of white matter glial cells, with several expressed at higher levels than found in control whole brain RNA.