BMP Signaling Goes Posttranscriptional in a microRNA Sort of Way

Aberrant microRNA (miRNA) expression correlates with human diseases such as cardiac disorders and cancer. Treatment of such disorders using miRNA-targeted therapeutics requires a thorough understanding of miRNA regulation in vivo. A recent paper in Nature by Davis et al. expands our understanding of miRNA biogenesis and maturation, elucidating a mechanism by which extracellular signaling directs cell differentiation via posttranscriptional regulation of miRNA expression

An Analysis of Putative Roles for the CCR4-NOT Deadenylase-Complex Subunit Regena (NOT2) in microRNA-Mediated Gene Silencing in \u3cem\u3eDrosophila Melanogaster\u3c/em\u3e

microRNAs (miRNAs) are one class of small non-coding ribonucleic acid (RNA) molecules essential to development and homeostasis in plants and animals. miRNAs silence gene expression through complementary base pairing with target gene messenger RNAs and association with the miRNA-induced silencing complex (miRISC). The identification and characterization of cellular factors required for miRNA-mediated gene silencing is incomplete. A forward genetic screen was carried out in Drosophila melanogaster to generate flies defective for gene silencing. Silencing was assayed by expression of a Green Fluorescent Protein (GFP) reporter fused to the Brd gene 3’ UTR, which is regulated by miRNAs. Genetic analysis revealed that the CCR4-NOT deadenylase-complex subunit Regena (NOT2) is required for miRNA-mediated silencing of the reporter. In addition, perturbation of Regena function altered Drosophila eye development and resulting adult eye morphology. miRNAs are thought to silence target gene expression through a combination of translational repression and target mRNA degradation, though the detailed mechanism of this process is a matter of controversy. Novel genetic reagents to explore miRNA function in vivo have been generated and characterized. Ongoing efforts aim to explore whether Regena is required to silence other miRNA targets in vivo, and whether Regena is required for miRNA-mediated gene silencing at different stages of the Drosophila life cycle. Elucidation of the lesion in the Regena (NOT2) gene and the molecular nature of GFP reporter silencing will contribute to an understanding of the mechanism of miRNA-mediated gene silencing in vivo

A microRNA Imparts Robustness against Environmental Fluctuation during Development

The microRNA miR-7 is perfectly conserved from annelids to humans, and yet some of the genes that it regulates in Drosophila are not regulated in mammals. We have explored the role of lineage restricted targets, using Drosophila , in order to better understand the evolutionary significance of microRNA-target relationships. From studies of two well characterized developmental regulatory networks, we find that miR-7 functions in several interlocking feedback and feedforward loops, and propose that its role in these networks is to buffer them against perturbation. To directly demonstrate this function for miR-7, we subjected the networks to temperature fluctuation and found that miR-7 is essential for the maintenance of regulatory stability under conditions of environmental flux. We suggest that some conserved microRNAs like miR-7 may enter into novel genetic relationships to buffer developmental programs against variation and impart robustness to diverse regulatory networks

From Observers to Participants: Joining the Scientific Community

In this essay, we have integrated the voices of our mentors and students to explore 45 years of undergraduate research experiences and their role in shaping our scientific community. In considering our collective experiences, we see undergraduate involvement in research as a rich source of community development, one that has both touched our lives and influenced our teaching

A Role for Actin, Cdc1p, and Myo2p in the Inheritance of Late Golgi Elements in \u3cem\u3eSaccharomyces cerevisiae\u3c/em\u3e

In Saccharomyces cerevisiae, Golgi elements are present in the bud very early in the cell cycle. We have analyzed this Golgi inheritance process using fluorescence microscopy and genetics. In rapidly growing cells, late Golgi elements show an actin-dependent concentration at sites of polarized growth. Late Golgi elements are apparently transported into the bud along actin cables and are also retained in the bud by a mechanism that may involve actin. A visual screen for mutants defective in the inheritance of late Golgi elements yielded multiple alleles of CDC1. Mutations in CDC1 severely depolarize the actin cytoskeleton, and these mutations prevent late Golgi elements from being retained in the bud. The efficient localization of late Golgi elements to the bud requires the type V myosin Myo2p, further suggesting that actin plays a role in Golgi inheritance. Surprisingly, early and late Golgi elements are inherited by different pathways, with early Golgi elements localizing to the bud in a Cdc1p- and Myo2p-independent manner. We propose that early Golgi elements arise from ER membranes that are present in the bud. These two pathways of Golgi inheritance in S. cerevisiae resemble Golgi inheritance pathways in vertebrate cells

Guidelines for Field Surveys of the Quality of Medicines: A Proposal

Paul Newton and colleagues propose guidelines for conducting and reporting field surveys of the quality of medicines

Alcator C-Mod: research in support of ITER and steps beyond

This paper presents an overview of recent highlights from research on Alcator C-Mod. Significant progress has been made across all research areas over the last two years, with particular emphasis on divertor physics and power handling, plasma–material interaction studies, edge localized mode-suppressed pedestal dynamics, core transport and turbulence, and RF heating and current drive utilizing ion cyclotron and lower hybrid tools. Specific results of particular relevance to ITER include: inner wall SOL transport studies that have led, together with results from other experiments, to the change of the detailed shape of the inner wall in ITER; runaway electron studies showing that the critical electric field required for runaway generation is much higher than predicted from collisional theory; core tungsten impurity transport studies reveal that tungsten accumulation is naturally avoided in typical C-Mod conditions.United States. Department of Energy (DE-FC02-99ER54512-CMOD)United States. Department of Energy (DE-AC02-09CH11466)United States. Department of Energy (DE-FG02-96ER-54373)United States. Department of Energy (DE-FG02-94ER54235

Different Mi-2 Complexes for Various Developmental Functions in Caenorhabditis elegans

Biochemical purifications from mammalian cells and Xenopus oocytes revealed that vertebrate Mi-2 proteins reside in multisubunit NuRD (Nucleosome Remodeling and Deacetylase) complexes. Since all NuRD subunits are highly conserved in the genomes of C. elegans and Drosophila, it was suggested that NuRD complexes also exist in invertebrates. Recently, a novel dMec complex, composed of dMi-2 and dMEP-1 was identified in Drosophila. The genome of C. elegans encodes two highly homologous Mi-2 orthologues, LET-418 and CHD-3. Here we demonstrate that these proteins define at least three different protein complexes, two distinct NuRD complexes and one MEC complex. The two canonical NuRD complexes share the same core subunits HDA-1/HDAC, LIN-53/RbAp and LIN-40/MTA, but differ in their Mi-2 orthologues LET-418 or CHD-3. LET-418 but not CHD-3, interacts with the Krüppel-like protein MEP-1 in a distinct complex, the MEC complex. Based on microarrays analyses, we propose that MEC constitutes an important LET-418 containing regulatory complex during C. elegans embryonic and early larval development. It is required for the repression of germline potential in somatic cells and acts when blastomeres are still dividing and differentiating. The two NuRD complexes may not be important for the early development, but may act later during postembryonic development. Altogether, our data suggest a considerable complexity in the composition, the developmental function and the tissue-specificity of the different C. elegans Mi-2 complexes