title: Expression of the H-ras proto-oncogene is controlled by alternative splicing.
abstract: 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.
authors.affiliation: Department of Cell Genetics, Genentech, Inc., South San Francisco, California 94080.
authors.forename: J B
authors.initials: JB
authors.lastname: Cohen
authors.forename: S D
authors.initials: SD
authors.lastname: Broz
authors.forename: A D
authors.initials: AD
authors.lastname: Levinson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D009154:Mutation; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)