Regulation of eukaryotic messenger RNA turnover
ABSTRACT We have demonstrated the existence of multiple mRNA binding proteins that interact specifically with defined regions in posttranscriptionally regulated mRNAs. These domains appear to be destabilizers whose function can be attenuated by the interaction with the specific binding proteins. Thus, the ability to alter mRNA decay rates on demand, given different environmental or intracellular conditions, appears to be mediated by controlling the localization, activity, and overall function of the cognate binding protein. Based on our limited experience, we predict that most, if not all, of similarly regulated mRNAs will ultimately be found to interact with regulatory mRNA binding proteins. Under conditions whereby the mRNA binding proteins are constitutively active (e.g., tumor cell lines), abnormal mRNA decay will result, with accumulation and overtranslation. Such appears to be the case for cytokines and possibly amyloid protein precursor mRNAs in cancer and Alzheimer's disease, respectively. Conversely, mutagenesis of these critical 3' untranslated region elements will likely have comparable deleterious effects on the regulation of gene expression. To the extent that such derangements exist in human disease, attention to understanding the mechanistic detail at this level may provide insights into the development of appropriate therapeutics or treatment strategies.
SourceAvailable from: Barbara Blacklaws
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ABSTRACT: Interleukin (IL)-21 was recently dis- covered using a functional cloning approach based on expression of its receptor. It is similar in domain organization and primary sequence to IL-2 and IL-15. Like these cytokines, IL-21 uses the com- mon chain of the IL-2/15 receptor, which forms a heterodimeric receptor complex with IL-21R. IL-21 is produced by activated T cells, and it in- fluences proliferation of T and B cells and cytolytic activity of natural killer cells. The elucidation of the unique biological effects of IL-21 represents an intense area of interest in current cytokine biology. J. Leukoc. Biol. 72: 856-863; 2002.Trends in Microbiology 08/1998; 6(8). DOI:10.1016/S0966-842X(98)01330-4 · 9.81 Impact Factor
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ABSTRACT: Estuarine turbidity maximum, numerical modeling, settling velocity, stratification The spatial and temporal distribution of suspended material in an Estuarine Turbidity Maxima (ETM) is primarily controlled by particle settling velocity, tidal mixing, shear-stress thresholds for resuspension, and sediment supply. We vary these parameters in numerical experiments of an idealized two-dimensional (x-z) estuary to demonstrate their affects on the development and retention of particles in an ETM. Parameters varied are the settling velocity (0.01, 0.1, and 0.5 mm/s), tidal amplitude (0.4 m 12 hour tide and 0.3 to 0.6 m 14 day spring neap cycle), and sediment availability (spatial supply limited or unlimited; and temporal supply as a riverine pulse during spring vs. neap tide). Results identify that particles with a low settling velocity are advected out of the estuary and particles with a high settling velocity provide little material transport to an ETM. Particles with an intermediate settling velocity develop an ETM with the greatest amount of material retained. For an unlimited supply of sediment the ETM and limit of salt intrusion co-vary during the spring neap cycle. The ETM migrates landward of the salt intrusion during spring tides and seaward during neap tides. For limited sediment supply the ETM does not respond as an erodible pool of sediment that advects landward and seaward with the salt front. The ETM is maintained seaward of the salt intrusion and controlled by the locus of sediment convergence in the bed. For temporal variability of sediment supplied from a riverine pulse, the ETM traps more sediment if the pulse encounters the salt intrusion at neap tides than during spring tides.