It is often found that tumors have chromosomal translocation, especially in hematological malignancies. A specific chromosomal translocation is related to a specific type of disease. Recent studies have revealed that genetic aberrations originated from these chromosomal tr ...
The hammerhead ribozyme was discovered as a self-cleaving RNA molecule in certain plant viroids and satellite RNAs (1). Shortly after its conserved features were defined (2,3), the hammerhead was shown to be able to act as a true enzyme, cleaving multiple substrates in a bimolecular reaction (4). ...
The significance of blood vessel formation (angiogenesis) for the growth of solid tumors and ultimately their metastatic spread has gained wide acceptance. The close relationship between tumor angiogenesis and metastasis has been demonstrated in a series of correlative clinical ...
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that results in dementia, and ultimately in the death of its victims. In the United States, AD is the fourth leading cause of death, and without a forseeable means of prevention, or effective treatment this will likely incre ...
The discovery of enzymatic RNA molecules, termed ribozymes (1,2), fundamentally changed our view of the function of RNA in chemistry, biology, and medicine. Naturally occurring enzymatic RNA molecules catalyze sequence-specific RNA processing. The sequence specificity is dete ...
The enzymatic activity of RNA molecules has been a source of surprises ever since 1981 when Cech discovered this new aspect of RNA function (1,2). Its role as messenger and structural component in the translational process was suddenly transcended, and it is now evident that various RNA molecules ...
The study of cellular function of a particular gene can be advanced by either specifically eliminating or blocking the function of its gene product. Although antisense RNA has frequently been used for this purpose, the hammerhead ribozyme has recently drawn a great deal of attention due to its po ...
The development of efficient methods for manipulation of cell-specific gene expression in vivo is of great value for gaining new insights into complex biological systems, and for advancing gene therapy for human diseases. Transcript-specific downregulation of RNA levels and activ ...
RNase P is an enzyme that cleaves tRNA precursors to generate the 5′ termini of mature tRNAs (1). Recently, the author developed a method for specific inactivation of any RNA using human RNase P (2). This method involves the design of a small RNA, known as external guide sequence (EGS). EGS RNA, when complexed w ...
Most human diseases are a result of the dysfunction of cellular genes or a result of the invasion of cells by foreign genetic materials. Blocking disease-causing genes from making the proteins they specify is a strategy for combating disease processes. Antisense and ribozyme are two widely kn ...
Inactivation of gene expression by antisense mechanisms in general and by ribozymes in particular show great promise as a research tool as well as therapeutic agent in selectively reducing mRNA species and thus decreasing subsequent protein synthesis (for reviews see refs. 1 and 2).
A number of different approaches may be taken to show the effects of ribozymes in cells, yet they all have shortcomings. One major difficulty is that the concentration of target RNAs in cells is often very low. This is confounded by the fact that the cleavage products are generally degraded very quickly ...
Hepatitis delta virus (HDV) is an infectious, subviral, pathogen that is associated with a high incidence of fulminant hepatitis in humans. It consists of a closed-circular, single-stranded, RNA genome of about 1700 nucleotides in length that is replicated by a rolling-circle mechanism ( ...
The minimum catalytic center of (-)s TRSV was identified, biochemically characterized and named the hairpin ribozyme (1, 2). Following initial identification of the minimum catalytic sequence, we identified a trans-catalytic reaction and biochemically characterized this rea ...
The development of acquired immunodeficiency syndrome (AIDS) generally takes of the order of ten years with no effective therapy currently available (1,2). HIV, the causative agent, exhibits tropism for CD4+ T-lymphocytes, the primary targets for HIV infection in vivo. Infection of these ...
Expression of DNA methyltransferases (MTases) in yeast, which has a naturally unmethylated genome, enables the study of chromatin structure in intact cells. Initial studies, employing in vivo expression of dam MTase, which catalyzes the production of N6-methyladenine (6meA) at GATC s ...
Short (153–350 bp) DNA fragments containing single nucleosome cores have been employed for investigation of a variety of topics, including binding of regulatory transcription factors to nucleosomes (1) and mechanism of transcription of nucleosomal templates (2). The major advant ...
It has become increasingly clear over the last decade that chromatin structure and gene regulation are intricately intertwined. Different regulatory states of a given gene are frequently accompanied by changes in nuclease hypersensitive sites and nucleosome positioning (1–4). C ...
Gene expression is regulated by complex mechanisms involving dynamic interactions between cis-acting elements and trans-acting factors in a highly structured chromatin environment. Investigations of protein/DNA interactions in vitro may not have relevance to a living cell s ...
General remodeling of chromatin is associated with events determining cell fate and the expression of specific genetic programs (1,2). In almost every case there is a tight link between these chromatin remodeling events and a drastic modification of the cell cycle parameters. One of the most s ...