Translational regulation of gene expression

A report on the Cold Spring Harbor Laboratory meeting 'Translational Control', Cold Spring Harbor, USA, 7-12 September 2004.     

Hormonal regulation of gene expression

The involvement of plant hormones in the regulation of gene expression is well-recognized. Current research using molecular approaches has resulted in the isolation and characterization of a number of hormone-responsive genes and cDNAs. These genes are proving to be valuable molecular probes to study the mode of action of plant hormones. This review will briefly describe some recent molecular data from selected hormone-responsive plant systems. Results of these studies indicate potential complexity in the regulation of these genes. These results and future challenges are discussed.     

Nutritional regulation of gene expression

Summary The human genome has now been mapped with a complete sequence to follow shortly. The race is on to apply the vast amount of information contained in the billions of base-pairs. Concurrently, there is an increased demand from the public for perceived natural products. The nutritional supplement and pharmaceutical industries are broadening their product lines to meet this ever-increasing demand. As the genetic basis of disease becomes more evident, it is clear that the two industries will be forced to turn their attention to nutrients affecting gene expression. Such nutritional regulators of gene expression, or genomeceuticals (Brudnak, 2001), have enormous potential for therapeutic and prophylactic applications in both industries by affecting the integrity and expression of genes. However, there are caveats to this application, which if unheeded, may have disastrous results. This paper explores the idea behind the burgeoning area of genomeceuticals as well as some potential pit-falls that this novel area harbors. Representative examples are presented with a subsequent discussion focusing on the specifics of the application. Calculations based on: mw of GlcNAc · HCl=215.64, mw GlcNAc=179.18. Given: an infusion rate of 15 μM/Kg/min, 15 μM of GlcNAc=2.68 mg, and GHCl (glucosamine hydrochloride) is 83% GlcNAc.     

Temporal regulation of gene expression

Molecular biology gives a static--not a dynamic--vision of the mechanisms regulating gene expression. Genetics already gave to time a limited place in the explanation of living phenomena. Such a static vision is supported by the techniques--such as X-ray crystallography--used by the biologists. However time is an important parameter in the control of gene expression during the cellular response to external signals, during life and aging of organisms or even in the succession of living forms which takes place in evolution. Models are slowly moving, due to the eruption of new technologies giving access to the fast events which occur inside living cells. A new dynamic vision is progressively replacing the old one. The consequences of these changes on the form of the future biology remain still unknown.     

Plasmid-encoded regulation of colicin E1 gene expression.

A plasmid-encoded factor that regulates the expression of the colicin E1 gene was found in molecular cloning experiments. The 2,294-base-pair AvaII fragment of the colicin E1 plasmid (ColE1) carrying the colicin E1 structural gene and the promoter-operator region had the same information with respect to the repressibility and inducibility of colicin E1 synthesis as the original ColE1 plasmid. An operon fusion was constructed between the 204-bp fragment containing the colicin E1 promoter-operator and xylE, the structural gene for catechol 2,3-dioxygenase encoded on the TOL plasmid of Pseudomonas putida. The synthesis of the dioxygenase from the resulting plasmid occurred in recA+, but not in recA- cells and was derepressed in the recA lexA(Def) double mutant. These results indicate that the ColE1 plasmid has no repressor gene for colicin E1 synthesis and that the lexA protein functions as a repressor. Colicin E1 gene expression was adenosine 3',5'-phosphate (cAMP) dependent. Upon the removal of two PvuII fragments (2,000 bp in length) from the ColE1 plasmid, the induced synthesis of colicin E1 occurred in the adenylate-cyclase mutant even without cAMP. The 3,100-bp Tth111I fragment of the ColE1 plasmid cloned on pACYC177 restored the cAMP dependency of the deleted ColE1 plasmid. Since the deleted fragments correspond to the mobility region of ColE1, the cAMP dependency of the gene expression should be somehow related to the plasmid mobilization function.     

Androgenic regulation of hepatic gene expression

Androgen-dependent synthesis of alpha 2u globulin in the rat liver has been used in our laboratory as a model for studying the effect of sex hormones on hepatic gene expression. alpha 2u Globulin is a group of low molecular weight (Mr approximately 18,000) male specific urinary proteins synthesized and secreted by hepatocytes. In the male rat hepatic synthesis of alpha 2u globulin begins at puberty (approximately 40 days), reaches a peak level (approximately 20 mg/day) at about 75 days and declines during old age. Androgens can induce alpha 2u globulin in ovariectomized female rats in vivo and in the liver perfusion system in vitro. However, both prepubertal and senescent (greater than 800 days) male rats not only do not produce alpha 2u globulin but are also refractory to androgen administration. alpha 2u Globulin is coded by a multigene family comprising about 20-30 gene copies per haploid genome. All of these gene copies seem to express translationally active mRNAs giving rise to individual isoforms of alpha 2u globulin. Appearance and disappearance of the cytoplasmic androgen-binding protein (CAB) correlates with the androgen responsiveness of hepatocytes. Photoaffinity labeling of the hepatic cytosol shows that the biologically active binding protein, found in the cytosol of the mature male rat liver, has a molecular weight of 31 kDa. A molecular transition of the 31-kDa CAB to a biologically inactive 29-kDa form may be the basis of hepatic androgen insensitivity during prepuberty and senescence.     

人促红细胞生成素的表达调控

人促红细胞生成素是控制红细胞生长发育的一种重要的细胞因子,在人体内具发育阶段异性、分泌的诱导性等特点,是研究真核基因表达的理想模型。本文从细胞水平的调控、基因结构以及基因３′和５′侧翼序列的调控元件对人促红细胞生成素表达的影响作用进行了讨论。