Mature microRNA-binding protein QKI suppresses extracellular microRNA let-7b release.

Argonaute (AGO), a component of RNA-induced silencing complexes (RISCs), is a representative RNA-binding protein (RBP) known to bind with mature microRNAs (miRNAs) and is directly involved in post-transcriptional gene silencing. However, despite the biological significance of miRNAs, the roles of other miRNA-binding proteins (miRBPs) remain unclear in the regulation of miRNA loading, dissociation from RISCs and extracellular release. In this study, we performed protein arrays to profile miRBPs and identify 118 RBPs that directly bind to miRNAs.

Targeting of CYP2E1 by miRNAs in alcohol-induced intestine injury.

Although binge alcohol-induced gut leakage has been studied extensively in the context of reactive oxygen species-mediated signaling, it was recently revealed that post-transcriptional regulation plays an essential role as well. Ethanol (EtOH)-inducible cytochrome P450-2E1 (CYP2E1), a key enzyme in EtOH metabolism, promotes alcohol-induced hepatic steatosis and inflammatory liver disease, at least in part by mediating changes in intestinal permeability. For instance, gut leakage and elevated intestinal permeability to endotoxins have been shown to be regulated by enhancing CYP2E1 mRNA and CYP2E1 protein levels.

Mature microRNA-binding protein QKI promotes microRNA-mediated gene silencing.

Although Argonaute (AGO) proteins have been the focus of microRNA (miRNA) studies, we observed AGO-free mature miRNAs directly interacting with RNA-binding proteins, implying the sophisticated nature of fine-tuning gene regulation by miRNAs. To investigate microRNA-binding proteins (miRBPs) globally, we analyzed PAR-CLIP data sets to identify RBP quaking (QKI) as a novel miRBP for let-7b. Potential existence of AGO-free miRNAs were further verified by measuring miRNA levels in genetically engineered AGO-depleted human and mouse cells.

Enzyme-responsive macrocyclic metal complexes for biomedical imaging.

Metal chelator-based contrast agents are used as tumor navigators for cancer diagnosis. Although approved metal chelators show excellent contrast performance in magnetic resonance imaging (MRI), large doses are required for cancer diagnoses due to rapid clearance and nonspecific accumulation throughout the body, which can compromise safety. The present study describes an enzyme-responsive metal delivery system, in which enzyme overexpressed in the tumor microenvironment selectively activates the tumor uptake of gadolinium (Gd).

Blood-declustering excretable metal clusters assembled in DNA matrix.

We report polymeric DNA-supported gold clusters that achieve interparticle plasmon-coupling, generate immunotherapeutic effects at the tumor tissue, but decluster in the bloodstream. As immunostimulating DNA, we used polyCpG DNA, which could act as a supporting matrix for metal clusters, enabling the clusters to decluster in the bloodstream. We constructed polyCpG-supported gold nanoclusters (AuPCN).

Profiling of RNA-binding Proteins Interacting With Glucagon and Adipokinetic Hormone mRNAs.

Objective: Glucagon in mammals and its homolog (adipokinetic hormone [AKH] in ) are peptide hormones which regulate lipid metabolism by breaking down triglycerides. Although regulatory mechanisms of glucagon and AKH expression have been widely studied, post-transcriptional gene expression of glucagon has not been investigated thoroughly. In this study, we aimed to profile proteins binding with messenger RNA (mRNA) in mouse and mRNA in Drosophila.

NEAT1 is essential for metabolic changes that promote breast cancer growth and metastasis.

Accelerated glycolysis is the main metabolic change observed in cancer, but the underlying molecular mechanisms and their role in cancer progression remain poorly understood. Here, we show that the deletion of the long noncoding RNA (lncRNA) Neat1 in MMTV-PyVT mice profoundly impairs tumor initiation, growth, and metastasis, specifically switching off the penultimate step of glycolysis. Mechanistically, NEAT1 directly binds and forms a scaffold bridge for the assembly of PGK1/PGAM1/ENO1 complexes and thereby promotes substrate channeling for high and efficient glycolysis.

Accumulation of Mitochondrial RNA Is Associated with Cellular Senescence.

Post-transcriptional gene regulation is an important step in the regulation of eukaryotic gene expression. Subcellular compartmentalization of RNA species plays a crucial role in the control of mRNA turnover, spatial restriction of protein synthesis, and the formation of macromolecular complexes. Although long noncoding RNAs (lncRNAs) are one of the key regulators of post-transcriptional gene expression, it is not heavily studied whether localization of lncRNAs in subcellular organelles has functional consequences.

Tannic acid-functionalized boron nitride nanosheets for theranostics.

Here, we report a tannic acid-Fe coordination complex coating that confers magnetic resonance imaging (MRI) theranostic properties to inert nanomaterials. Boron nitride nanosheets (BNS), which lack magnetic field and light responsiveness, were used as a model nonfunctional nanomaterial. Among various catechol derivatives tested (i.

Biochemical reprogramming of tumors for active modulation of receptor-mediated nanomaterial delivery.

Here we report that reactive oxygen species (ROS) can reprogram cancer cells to increase the expression of specific receptors and modulate the delivery of nanomaterials. Gold and γ-polyglutamic acid (γ-PGA) hybrid nanoparticles (PGANP) were prepared via a facile single-step process. Gold nanoclusters in PGANP were dispersed within the tangled γ-PGA matrix of the nanoparticles.

A Microbial Siderophore-Inspired Self-Gelling Hydrogel for Noninvasive Anticancer Phototherapy.

Microbial carboxyl and catechol siderophores have been shown to have natural iron-chelating abilities, suggesting that hyaluronic acid (HA) and the catechol compound, gallic acid (GA), may have iron-coordinating activities. Here, a photoresponsive self-gelling hydrogel that was both injectable and could be applied to the skin was developed on the basis of the abilities of HA and GA to form coordination bonds with ferric ions (Fe). The conjugate of HA and GA (HA-GA) instantly formed hydrogels in the presence of ferric ions and showed near-infrared (NIR)-responsive photothermal properties.

Light-switchable systems for remotely controlled drug delivery.

Light-switchable systems have recently received attention as a new mode of remotely controlled drug delivery. In the past, a multitude of nanomedicine studies have sought to enhance the specificity of drug delivery to target sites by focusing on receptors overexpressed on malignant cells or environmental features of diseases sites. Despite these immense efforts, however, there are few clinically available nanomedicines.