CSDE1 promotes miR-451 biogenesis.

MicroRNAs are sequentially processed by RNase III enzymes Drosha and Dicer. miR-451 is a highly conserved miRNA in vertebrates which bypasses Dicer processing and instead relies on AGO2 for its maturation. miR-451 is highly expressed in erythrocytes and regulates the differentiation of erythroblasts into mature red blood cells.

The challenges of ethical deliberation in palliative care settings: A descriptive study.

Objective: Inadequate deliberation processes about ethical problems occurring in palliative care settings may negatively impact both patients and healthcare professionals. Better knowledge of the palliative care professionals' practices regarding such processes could help identify specific education needs to improve the quality of palliative care in the context of complex ethical situations. Therefore, this descriptive study aimed to (1) examine ethical deliberation processes in interprofessional teams in five palliative care settings; (2) identify organizational factors that constrain such processes; and (3) based on this knowledge, identify priority education needs for future and current palliative care professionals.

Long non-coding RNAs and transposable elements: A functional relationship.

Long non-coding RNAs (lncRNAs) have become increasingly important in the past decade. They are known to regulate gene expression and to interact with chromatin, proteins and other coding and non-coding RNAs. The study of lncRNAs has been challenging due to their low expression and the lack of tools developed to adapt to their particular features.

CSDE1 controls gene expression through the miRNA-mediated decay machinery.

In animals, miRNAs are the most prevalent small non-coding RNA molecules controlling posttranscriptional gene regulation. The Argonaute proteins (AGO) mediate miRNA-guided gene silencing by recruiting multiple factors involved in translational repression, deadenylation, and decapping. Here, we report that CSDE1, an RNA-binding protein linked to stem cell maintenance and metastasis in cancer, interacts with AGO2 within miRNA-induced silencing complex and mediates gene silencing through its N-terminal domains.

Defend Thyself and Thy Offspring.

Three recent studies (Dodson and Kennedy, 2019; Lev et al., 2019; Ouyang et al., 2019) reveal that germ granule formation is necessary to protect germline-expressed genes from improper small RNA-mediated silencing.

A guide to microRNA-mediated gene silencing.

As an important regulator of gene expression in eukaryotes, microRNAs (miRNAs) have been subject to extensive research to understand their pleiotropic roles in development and pathological processes. Here, we review strategies that have been developed to map microRNA-target interactions and the most effective methods to attribute post-transcriptional gene regulation through miRNA-mediated silencing. We further discuss the importance of the biological context for silencing.

Somatic and Germline MicroRNAs Form Distinct Silencing Complexes to Regulate Their Target mRNAs Differently.

Animal germ cells possess a specific post-transcriptional regulatory context allowing the storage of maternal transcripts in the oocyte until their translation at a specific point in early development. As key regulators of gene expression, miRNAs repress translation mainly through mRNA destabilization. Thus, germline miRNAs likely use distinct ways to regulate their targets.

Crowding, Entropic Forces, and Confinement: Crucial Factors for Structures and Functions in the Cell Nucleus.

The view of the cell nucleus as a crowded system of colloid particles and that chromosomes are giant self-avoiding polymers is stimulating rapid advances in our understanding of its structure and activities, thanks to concepts and experimental methods from colloid, polymer, soft matter, and nano sciences and to increased computational power for simulating macromolecules and polymers. This review summarizes current understanding of some characteristics of the molecular environment in the nucleus, of how intranuclear compartments are formed, and of how the genome is highly but precisely compacted, and underlines the crucial, subtle, and sometimes unintuitive effects on structures and reactions of entropic forces caused by the high concentration of macromolecules in the nucleus.

Endothelial microRNAs regulating the NF-κB pathway and cell adhesion molecules during inflammation.

The surface of endothelial cells is covered with cell adhesion molecules, including E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM- 1) , that mediate the adhesion and extravasation of leukocytes and play pivotal roles in inflammatory response. microRNAs (miRNAs) regulate the expression of these important cell adhesion molecules through two distinct major mechanisms, namely via modulating the proinflammatory NF-κB pathway, which controls their transcription, and via directly targeting them. The present review highlights the role of various miRNAs in controlling the expression of E-selectin, ICAM-1, and VCAM-1: a type of regulation that can be harnessed for therapeutic prevention of inflammation-associated diseases such as atherosclerosis and sepsis.

p38 activation induces production of miR-146a and miR-31 to repress E-selectin expression and inhibit transendothelial migration of colon cancer cells.

Extravasation of circulating cancer cells determines their metastatic potential. This process is initiated by the adhesion of cancer cells to vascular endothelial cells through specific interactions between endothelial adhesion receptors such as E-selectin and their ligands on cancer cells. In the present study, we show that miR-146a and miR-181b impede the expression of E-selectin by repressing the activity of its transcription factor NF-κB, thereby impairing the metastatic potentials of colon cancer cells by decreasing their adhesion to, and migration through, the endothelium.

Phosphorylation of Argonaute proteins affects mRNA binding and is essential for microRNA-guided gene silencing .

Argonaute proteins associate with microRNAs and are key components of gene silencing pathways. With such a pivotal role, these proteins represent ideal targets for regulatory post-translational modifications. Using quantitative mass spectrometry, we find that a C-terminal serine/threonine cluster is phosphorylated at five different residues in human and In human, hyper-phosphorylation does not affect microRNA binding, localization, or cleavage activity of Ago2.

TEG-1 CD2BP2 controls miRNA levels by regulating miRISC stability in C. elegans and human cells.

MiRNAs post-transcriptionally regulate gene expression by recruiting the miRNA-induced silencing complex (miRISC) to target mRNAs. However, the mechanisms by which miRISC components are maintained at appropriate levels for proper function are largely unknown. Here, we demonstrate that Caenorhabditis elegans TEG-1 regulates the stability of two miRISC effectors, VIG-1 and ALG-1, which in turn affects the abundance of miRNAs in various families.

GW182-Free microRNA Silencing Complex Controls Post-transcriptional Gene Expression during Caenorhabditis elegans Embryogenesis.

MicroRNAs and Argonaute form the microRNA induced silencing complex or miRISC that recruits GW182, causing mRNA degradation and/or translational repression. Despite the clear conservation and molecular significance, it is unknown if miRISC-GW182 interaction is essential for gene silencing during animal development. Using Caenorhabditis elegans to explore this question, we examined the relationship and effect on gene silencing between the GW182 orthologs, AIN-1 and AIN-2, and the microRNA-specific Argonaute, ALG-1.

p38 and JNK pathways control E-selectin-dependent extravasation of colon cancer cells by modulating miR-31 transcription.

Extravasation of circulating cancer cells is a key event of metastatic dissemination that is initiated by the adhesion of cancer cells to vascular endothelial cells. It requires the interaction between adhesion receptors such as E-selectin present on endothelial cells and their ligands on cancer cells. Notably, E-selectin influences the metastatic potential of breast, bladder, gastric, pancreatic, and colorectal carcinoma as well as of leukemia and lymphoma.

The implication of microRNAs and endo-siRNAs in animal germline and early development.

Germ cells provide maternal mRNAs that are stored in the oocyte, and later translated at a specific time of development. In this context, gene regulation depends mainly on post-transcriptional mechanisms that contribute to keep maternal transcripts in a stable and translationally silent state. In recent years, small non-coding RNAs, such as microRNAs have emerged as key post-transcriptional regulators of gene expression.

Poly(A)-binding proteins are required for microRNA-mediated silencing and to promote target deadenylation in C. elegans.

Cytoplasmic poly(A)-binding proteins (PABPs) link mRNA 3' termini to translation initiation factors, but they also play key roles in mRNA regulation and decay. Reports from mice, zebrafish and Drosophila further involved PABPs in microRNA (miRNA)-mediated silencing, but through seemingly distinct mechanisms. Here, we implicate the two Caenorhabditis elegans PABPs (PAB-1 and PAB-2) in miRNA-mediated silencing, and elucidate their mechanisms of action using concerted genetics, protein interaction analyses, and cell-free assays.

The human decapping scavenger enzyme DcpS modulates microRNA turnover.

The decapping scavenger enzyme DcpS is known for its role in hydrolyzing the cap structure following mRNA degradation. Recently, we discovered a new function in miRNA degradation activation for the ortholog of DcpS in C. elegans.

Cystatin C for early detection of acute kidney injury after laparoscopic partial nephrectomy.

Introduction And Objectives: Mortality due to AKI has not changed significantly over the past 50 years. This is due in part to failure to detect early AKI and to initiate appropriate therapeutic measures. There is therefore a need to identify biomarkers that would improve the early detection of AKI.

Isolation of nuclei in media containing an inert polymer to mimic the crowded cytoplasm.

Within cells, the nucleus is surrounded by the cytoplasm which contains diffusible macromolecules at a high concentration (>100 mg/ml). When cells are broken to isolate nuclei by current methods these macromolecules are dispersed, and to reproduce the environment of nuclei in vivo more closely we have developed a method to isolate them in a medium where cytoplasmic macromolecules are replaced by an inert, volume-occupying polymer and which is essentially cation-free. Nuclei isolated by this method resemble closely those prepared by conventional procedures as seen by optical and electron microscopy, and their internal compartments (nucleoli, PML and Cajal bodies, transcription centers, and splicing speckles) and transcriptional activity are conserved.

IL-8 secretion in primary cultures of prostate cells is associated with prostate cancer aggressiveness.

Background: Chronic inflammation is believed to be a major factor in prostate cancer initiation and promotion and has been studied using prostate cancer cells and immortalized cell lines. However, little is known about the contribution of normal cells to the prostatic microenvironment and inflammation. We aim to study the contribution of normal prostate epithelial cells to prostate inflammation and to link the inflammatory status of normal cells to prostate cancer aggressiveness.

Mutations in conserved residues of the C. elegans microRNA Argonaute ALG-1 identify separable functions in ALG-1 miRISC loading and target repression.

microRNAs function in diverse developmental and physiological processes by regulating target gene expression at the post-transcriptional level. ALG-1 is one of two Caenorhabditis elegans Argonautes (ALG-1 and ALG-2) that together are essential for microRNA biogenesis and function. Here, we report the identification of novel antimorphic (anti) alleles of ALG-1 as suppressors of lin-28(lf) precocious developmental phenotypes.

The crowded nucleus.

The principles that determine the organization of the nucleus have become clearer in recent years, largely because of new insights into polymer, colloid, and soft-matter science. Macromolecules, together with the giant linear polymers that form the chromosomes, are confined at high concentrations within the nuclear envelope and their interactions are influenced strongly by short-range depletion or entropic forces which are negligible in dilute systems, in addition to the more familiar van der Waals, electrostatic, steric, hydrogen bonding, and hydrophobic forces. The studies described in this volume are consistent with the model that this complex and concentrated mixture of macromolecules is maintained in a delicate equilibrium by quite simple although unsuspected physicochemical principles.

The decapping scavenger enzyme DCS-1 controls microRNA levels in Caenorhabditis elegans.

In metazoans, microRNAs play a critical role in the posttranscriptional regulation of genes required for cell proliferation and differentiation. MicroRNAs themselves are regulated by a multitude of mechanisms influencing their transcription and posttranscriptional maturation. However, there is only sparse knowledge on pathways regulating the mature, functional form of microRNA.