Epigenetic dysregulation of eukaryotic initiation factor 3 subunit E (eIF3E) by lysine methyltransferase REIIBP confers a pro-inflammatory phenotype in t(4;14) myeloma.

REIIBP is a lysine methyltransferase aberrantly expressed through alternative promoter usage of NSD2 locus in t(4;14)-translocated multiple myeloma (MM). Clinically, t(4;14) translocation is an adverse prognostic factor found in approximately 15% of MM patients. The contribution of REIIBP relative to other NSD2 isoforms as a dependency gene in t(4;14)-translocated MM remains to be evaluated.

Sex Difference in Lower-limb Electromyography and Kinematics when Using Resistance Bands during a Barbell Back Squat.

The aim of this study was to compare the muscle activity of the gluteus medius (GMe), gluteus maximus (GMa), biceps femoris (BF), vastus lateralis (VL), vastus medialis (VM) and erector spinae (ES) as well as medial knee displacement (MKD) while using varying stiffness resistance bands (red: 1.68 kg; black: 3.31 kg; gold: 6.

Arl15 upregulates the TGFβ family signaling by promoting the assembly of the Smad-complex.

The hallmark event of the canonical transforming growth factor β (TGFβ) family signaling is the assembly of the Smad-complex, consisting of the common Smad, Smad4, and phosphorylated receptor-regulated Smads. How the Smad-complex is assembled and regulated is still unclear. Here, we report that active Arl15, an Arf-like small G protein, specifically binds to the MH2 domain of Smad4 and colocalizes with Smad4 at the endolysosome.

Pan-cancer pervasive upregulation of 3' UTR splicing drives tumourigenesis.

Most mammalian genes generate messenger RNAs with variable untranslated regions (UTRs) that are important post-transcriptional regulators. In cancer, shortening at 3' UTR ends via alternative polyadenylation can activate oncogenes. However, internal 3' UTR splicing remains poorly understood as splicing studies have traditionally focused on protein-coding alterations.

Arginase Signalling as a Key Player in Chronic Wound Pathophysiology and Healing.

Arginase (ARG) represents an important evolutionarily conserved enzyme that is expressed by multiple cell types in the skin. Arg acts as the mediator of the last step of the urea cycle, thus providing protection against excessive ammonia under homeostatic conditions through the production of L-ornithine and urea. L-ornithine represents the intersection point between the ARG-dependent pathways and the urea cycle, therefore contributing to cell detoxification, proliferation and collagen production.

An Epidermal-Specific Role for Arginase1 during Cutaneous Wound Repair.

Nonhealing wounds are a major area of unmet clinical need remaining problematic to treat. Improved understanding of prohealing mechanisms is invaluable. The enzyme arginase1 (ARG1) is involved in prohealing responses, with its role in macrophages best characterized.

The Polyamine Regulator AMD1 Upregulates Spermine Levels to Drive Epidermal Differentiation.

Maintaining tissue homeostasis depends on a balance between cell proliferation, differentiation, and apoptosis. Within the epidermis, the levels of the polyamines putrescine, spermidine, and spermine are altered in many different skin conditions, yet their role in epidermal tissue homeostasis is poorly understood. We identify the polyamine regulator, Adenosylmethionine decarboxylase 1 (AMD1), as a crucial regulator of keratinocyte (KC) differentiation.

Determination of isoform-specific RNA structure with nanopore long reads.

Current methods for determining RNA structure with short-read sequencing cannot capture most differences between distinct transcript isoforms. Here we present RNA structure analysis using nanopore sequencing (PORE-cupine), which combines structure probing using chemical modifications with direct long-read RNA sequencing and machine learning to detect secondary structures in cellular RNAs. PORE-cupine also captures global structural features, such as RNA-binding-protein binding sites and reactivity differences at single-nucleotide variants.

The Polyamine Putrescine Promotes Human Epidermal Melanogenesis.

Hyperpigmentary conditions can arise when melanogenesis in the epidermis is misregulated. Understanding the pathways underlying melanogenesis is essential for the development of effective treatments. Here, we report that a group of metabolites called polyamines are important in the control of melanogenesis in human skin.

Quantification of Melanosome Transfer Using Immunofluorescence Microscopy and Automated Image Analysis.

The study of skin pigmentation requires determining the rate of melanin production in melanocytes and quantifying the rate of melanosome transfer to keratinocytes. Here, we describe a method to quantify melanosome transfer using immunofluorescence microscopy coupled with automated image analysis of in vitro human melanocytes and keratinocytes in co-culture. In this method, the number of melanin capped keratinocyte nuclei is quantified.

Polyamine Regulator AMD1 Promotes Cell Migration in Epidermal Wound Healing.

Wound healing is a dynamic process involving gene-expression changes that drive re-epithelialization. Here, we describe an essential role for polyamine regulator AMD1 in driving cell migration at the wound edge. The polyamines, putrescine, spermidine, and spermine are small cationic molecules that play essential roles in many cellular processes.

MINDY1 Is a Downstream Target of the Polyamines and Promotes Embryonic Stem Cell Self-Renewal.

Embryonic stem cells have the ability to self-renew or differentiate and these processes are under tight control. We previously reported that the polyamine regulator AMD1 is critical for embryonic stem cell self-renewal. The polyamines putrescine, spermidine, and spermine are essential organic cations that play a role in a wide array of cellular processes.

5-Methylcytosine RNA Methylation in Arabidopsis Thaliana.

5-Methylcytosine (mC) is a well-characterized DNA modification, and is also predominantly reported in abundant non-coding RNAs in both prokaryotes and eukaryotes. However, the distribution and biological functions of mC in plant mRNAs remain largely unknown. Here, we report transcriptome-wide profiling of RNA mC in Arabidopsis thaliana by applying mC RNA immunoprecipitation followed by a deep-sequencing approach (mC-RIP-seq).

MicroRNA-31 promotes adverse cardiac remodeling and dysfunction in ischemic heart disease.

Rationale: Myocardial infarction (MI) triggers a dynamic microRNA response with the potential of yielding therapeutic targets.

Objective: We aimed to identify novel aberrantly expressed cardiac microRNAs post-MI with potential roles in adverse remodeling in a rat model, and to provide post-ischemic therapeutic inhibition of a candidate pathological microRNA in vivo.

Methods And Results: Following microRNA array profiling in rat hearts 2 and 14days post-MI, we identified a time-dependent up-regulation of miR-31 compared to sham-operated rats.

Histone modifications and p53 binding poise the p21 promoter for activation in human embryonic stem cells.

The high proliferation rate of embryonic stem cells (ESCs) is thought to arise partly from very low expression of p21. However, how p21 is suppressed in ESCs has been unclear. We found that p53 binds to the p21 promoter in human ESCs (hESCs) as efficiently as in differentiated human mesenchymal stem cells, however it does not promote p21 transcription in hESCs.

Cytoplasmic long noncoding RNAs are frequently bound to and degraded at ribosomes in human cells.

Recent footprinting studies have made the surprising observation that long noncoding RNAs (lncRNAs) physically interact with ribosomes. However, these findings remain controversial, and the overall proportion of cytoplasmic lncRNAs involved is unknown. Here we make a global, absolute estimate of the cytoplasmic and ribosome-associated population of stringently filtered lncRNAs in a human cell line using polysome profiling coupled to spike-in normalized microarray analysis.

Embryonic Stem Cells Exhibit mRNA Isoform Specific Translational Regulation.

The presence of multiple variants for many mRNAs is a major contributor to protein diversity. The processing of these variants is tightly controlled in a cell-type specific manner and has a significant impact on gene expression control. Here we investigate the differential translation rates of individual mRNA variants in embryonic stem cells (ESCs) and in ESC derived Neural Precursor Cells (NPCs) using polysome profiling coupled to RNA sequencing.

Analysis of mRNA Translation Rate in Mouse Embryonic Stem Cells.

Regulation of gene expression is essential to enable embryonic stem cells (ESCs) to either self-renew or to differentiate. Translational regulation of mRNA plays a major role in regulating gene expression and has been shown to be important for ESC differentiation. Sucrose gradients can be used to separate mRNAs based on the number of associated ribosomes and this can be used as a readout of the rate of translation.

Contrasting expression patterns of coding and noncoding parts of the human genome upon oxidative stress.

Oxidative stress (OS) is caused by an imbalance between pro- and anti-oxidant reactions leading to accumulation of reactive oxygen species within cells. We here investigate the effect of OS on the transcriptome of human fibroblasts. OS causes a rapid and transient global induction of transcription characterized by pausing of RNA polymerase II (PolII) in both directions, at specific promoters, within 30 minutes of the OS response.

Natriuretic peptide receptor 3 (NPR3) is regulated by microRNA-100.

Natriuretic peptide receptor 3 (NPR3) is the clearance receptor for the cardiac natriuretic peptides (NPs). By modulating the level of NPs, NPR3 plays an important role in cardiovascular homeostasis. Although the physiological functions of NPR3 have been explored, little is known about its regulation in health or disease.

Divergent LIN28-mRNA associations result in translational suppression upon the initiation of differentiation.

LIN28 function is fundamental to the activity and behavior of human embryonic stem cells (hESCs) and induced pluripotent stem cells. Its main roles in these cell types are the regulation of translational efficiency and let-7 miRNA maturation. However, LIN28-associated mRNA cargo shifting and resultant regulation of translational efficiency upon the initiation of differentiation remain unknown.

RPL39L is an example of a recently evolved ribosomal protein paralog that shows highly specific tissue expression patterns and is upregulated in ESCs and HCC tumors.

Ribosomal proteins (RPs) have been shown to be able to impart selectivity on the translating ribosome implicating them in gene expression control. Many ribosomal proteins are highly conserved and recently a number of ribosomal protein paralogs have been described in mammals. We examined the expression pattern of RPs in differentiating mouse Embryonic Stem Cells (ESCs), paying particular attention to the RP paralogs.

Commentary on: Hairless and the polyamine putrescine form a negative regulatory loop in the epidermis.

Polyamines are cationic amines essential for cellular proliferation. Recently, their role in hair follicle (HF) growth has started to be explored, but their exact function is still obscure. In the October issue of Experimental Dermatology, Luke et al.