Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously demonstrated that a point mutation in the last intron of the human H-ras oncogene causes a significant increase in its expression and transforming efficiency. Here we establish the basis of this phenomenon. Using gene reconstruction experiments, we have identified a negative-acting element in the intron that is completely inactivated by the mutation. The effects of other nucleotide alterations introduced into this region suggested that the negative element might constitute an alternative exon. Transcripts containing this putative exon were identified and S1 nuclease analysis confirmed that the mutation prevents their synthesis. The abundance of these transcripts is low, apparently due to message instability and/or defective processing. The predicted product of the alternative transcript is suggested to lack transforming potential. Our findings demonstrate that alternative splicing normally operates to suppress p21H-ras expression and that this negative control is abolished by a variety of mutations that interfere with this process.
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PMID:Expression of the H-ras proto-oncogene is controlled by alternative splicing. 266 64

A number of deletion mutants were isolated, including 5', 3', and internal deletions in the 5'-flanking region of the human cellular oncogene related to the Harvey sarcoma virus (c-H-ras), and their transforming activities were examined in NIH 3T3 cells. DNA sequences which could not be detected without losing transforming activity were localized to a relatively short stretch upstream of the region which showed homology to the 5'-flanking region of v-H-ras oncogene. S1 nuclease analysis indicated that there were two clusters of mRNA start sites at positions that were about 1,371 and 1,298 base pairs upstream of the first coding ATG. The minimum region required for promoter function was estimated to be a 51-base-pair-long (or less) DNA segment. The promoter was GC rich (78%) and did not contain the consensus sequences that are usually observed in PolII-directed promoters but contained a GC box within which one of the mRNA start sites was included. In addition, two sets of positive and negative elements seemed to be located between the promoter and the protein-coding region, which appeared to influence positively and negatively, respectively, the efficiency of transformation with the c-H-ras oncogene.
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PMID:Identification of the principal promoter sequence of the c-H-ras transforming oncogene: deletion analysis of the 5'-flanking region by focus formation assay. 367 Mar