Formation of the Moloney murine leukemia virus envelope mRNA involves the removal of a 5,185-base pairlong intron. Deletion analysis of two Moloney murine leukemia virus-derived expression vectors revealed the existence of two short regions within the viral intron which are required for the efficient formation of the spliced RNA species. One region was present upstream from the 3' splice junction, extended at least 85 nucleotides beyond the splice site, and was not more than 165 nucleotides long. As yeast polymerase II introns, the Moloney murine leukemia virus intron contains the sequence 5'-TACTAAC-3' 15 nucleotides upstream from the 3' splice site. A second region located in the middle of the intron, within a 560-nucleotide-long sequence, was also essential for formation of the spliced RNA species. The efficient splicing of the env mRNA in the absence of expression of viral genes raises the possibility that similar mechanisms are used to remove introns of (some) cellular genes.The coding regions of many eucaryotic genes are interrupted by stretches of noncoding DNA called intervening sequences or introns. The introns are transcribed as part of a precursor RNA and are subsequently removed in a process termed RNA splicing. A central problem in understanding the mechanism of splicing is identification of the RNA sequences responsible for the accurate removal of introns.Study of naturally occurring mutations and site-specific mutagenesis has shown that the nucleotides immediately adjacent to the splice junctions are required for splicing to occur. Deletions which removed the splice junctions of simiam virus 40 (SV40) small t antigen (27) or SV40 late mRNA (30, 55) abolished the synthesis of these RNA species. Similarly, globin genes from human thalassemic patients which contained mutations at the splice junctions did not generate the normally spliced RNA species (19,52,53). Site-specific mutagenesis has also shown that the nucleotides adjacent to the splice junctions are necessary for the formation of correctly spliced RNA species (20,37,61). The sequences adjacent to the splice junctions are strongly conserved, further demonstrating their functional importance (6,38,47 A large body of evidence indicates that the cis-acting regions required for efficient removal of introns exert their function through the formation of a secondary structure which brings the 5' and 3' splice junctions in close proximity. On the basis of nucleotide sequences of introns derived from fungal mitochondria and tetrahymena nuclear rRNA as well as Z. mays chloroplast mRNA, similar models of secondary structures that facilitate intron removal were proposed (10,16,36). Direct evidence for the role of a secondary structure in intron removal is provided by physical studies of the N. crassa mitochondrial rRNA intron (63), in vitro mutagenesis of the yeast tRNAleU intron (4), and analysis of cis mutations and their revertants in the yeast mitochondrial cytochrome b intron (59).Evidence for the role of sequences other than the consensus sequences...
These results suggest that HLTF methylation may play a crucial role in the early stages of gastric carcinogenesis in patients with family histories and may be a valuable susceptible marker for the risk of gastric cancer in individuals with family histories.
A novel disposable transnasal esophagoscope, the E.G. Scan (IntroMedic Co. Ltd., Seoul, Korea), was developed for the evaluation of esophageal diseases while eliminating the inconvenience associated with sterilization, portability, patient monitoring, complications, and the economic burden of sedation. The feasibility, safety, and tolerability of the first version of the E.G. Scan was evaluated in this pilot study. Nasal esophagoscopy was performed successfully in 46 patients with known or suspected esophageal diseases. At least 50% of the Z-line was visualized by the E.G. Scan in 38 (82.6%) of 46 patients. Abnormalities were identified in 27 patients: erosive esophagitis (n=18), Barrett's esophagus (n=1), esophageal varices (n=7), and esophageal candidiasis (n=1). Nasal pain was absent or mild in most patients, and adverse events were not observed. Further technical improvement of the E.G. Scan would increase the diagnostic usefulness in future clinical practice.
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