11 research outputs found

    Systematic Analysis of Cis-Elements in Unstable mRNAs Demonstrates that CUGBP1 Is a Key Regulator of mRNA Decay in Muscle Cells

    Get PDF
    BACKGROUND: Dramatic changes in gene expression occur in response to extracellular stimuli and during differentiation. Although transcriptional effects are important, alterations in mRNA decay also play a major role in achieving rapid and massive changes in mRNA abundance. Moreover, just as transcription factor activity varies between different cell types, the factors influencing mRNA decay are also cell-type specific. PRINCIPAL FINDINGS: We have established the rates of decay for over 7000 transcripts expressed in mouse C2C12 myoblasts. We found that GU-rich (GRE) and AU-rich (ARE) elements are over-represented in the 3'UTRs of short-lived mRNAs and that these mRNAs tend to encode factors involved in cell cycle and transcription regulation. Stabilizing elements were also identified. By comparing mRNA decay rates in C2C12 cells with those previously measured for pluripotent and differentiating embryonic stem (ES) cells, we identified several groups of transcripts that exhibit cell-type specific decay rates. Further, whereas in C2C12 cells the impact of GREs on mRNA decay appears to be greater than that of AREs, AREs are more significant in ES cells, supporting the idea that cis elements make a cell-specific contribution to mRNA stability. GREs are recognized by CUGBP1, an RNA-binding protein and instability factor whose function is affected in several neuromuscular diseases. We therefore utilized RNA immunoprecipitation followed by microarray (RIP-Chip) to identify CUGBP1-associated transcripts. These mRNAs also showed dramatic enrichment of GREs in their 3'UTRs and encode proteins linked with cell cycle, and intracellular transport. Interestingly several CUGBP1 substrate mRNAs, including those encoding the myogenic transcription factors Myod1 and Myog, are also bound by the stabilizing factor HuR in C2C12 cells. Finally, we show that several CUGBP1-associated mRNAs containing 3'UTR GREs, including Myod1, are stabilized in cells depleted of CUGBP1, consistent with the role of CUGBP1 as a destabilizing factor. CONCLUSIONS: Taken together, our results systematically establish cis-acting determinants of mRNA decay rates in C2C12 myoblast cells and demonstrate that CUGBP1 associates with GREs to regulate decay of a wide range of mRNAs including several that are critical for muscle development

    Use of Biotechnology in Forestry Breeding Programs for Natural Resources and Biodiversity Conservation: Creating Super Trees for the Future

    No full text
    Owing to the increasing human population and the increasing global demand for wood, its consumption is exceeding the natural rate of regeneration in many areas worldwide. Despite only 3% of the world’s forested land is plantation forest, plantations are highly productive; and with further improvement in genetic composition of planting stock as well as applying biotechnology, additional productivity increases can be obtained. For this reason, it is necessary to enrich traditional breeding programs with biotechnological tools able to increase the quantity and quality of the forestry plants produced. FAO’s definition of forest biotechnology encompasses different techniques for cloning forest trees. Forestry companies are currently considering clonal propagation as a good source of forestry plants. Clonal propagation can be achieved by various means: grafting, rooting of cuttings, coppicing, or in vitro propagation. Several methods of clonal propagation are being practiced with conifers. Along this chapter, a summary of some of the different approaches to improve Pinus spp. clonal propagation will be described, particularly those made in our laboratory

    Systems biology of lupus: Mapping the impact of genomic and environmental factors on gene expression signatures, cellular signaling, metabolic pathways, hormonal and cytokine imbalance, and selecting targets for treatment

    No full text

    Three decades of low-dose methotrexate in rheumatoid arthritis: Can we predict toxicity?

    No full text

    How frequent is altered gene expression among susceptibility genes to human complex disorders?

    No full text

    Elektrische Momente von Molekeln

    No full text
    corecore