       Document 0764
 DOCN  M9460764
 TI    Frameshift mutations in the v-src gene of avian sarcoma virus act in cis
       to specifically reduce v-src mRNA levels.
 DT    9404
 AU    Simpson SB; Stoltzfus CM; Department of Microbiology, University of
       Iowa, Iowa City 52242.
 SO    Mol Cell Biol. 1994 Mar;14(3):1835-44. Unique Identifier : AIDSLINE
       MED/94158855
 AB    A portion of the avian sarcoma virus (ASV) primary RNA transcripts is
       alternatively spliced in chicken embryo fibroblast cells to two
       different messages, the src and env mRNAs. Frameshift mutations of the
       viral genome causing premature translation termination within the src
       gene result in a decreased steady-state level of the src mRNA. In marked
       contrast, frameshift mutations at various positions of the env gene do
       not decrease the level of the env mRNA. We show that the src gene
       product is not required in trans for splicing and accumulation of src
       mRNA. Conversely, the truncated Src proteins do not act negatively in
       trans to decrease specifically the levels of src mRNA. Taken together,
       these results indicate that the frameshift mutations act in cis to
       reduce src mRNA levels. A double mutant with a lesion in the src
       initiator AUG and a frameshift within the src gene demonstrated
       wild-type RNA levels, indicating that the src mRNA must be recognized as
       a translatable mRNA for the effect on src mRNA levels to occur. Our
       results indicate that the reduced levels do not result from decreased
       cytoplasmic stability of the mature src mRNA. We also show that the src
       gene frameshift mutations affect src mRNA levels when expressed from
       intronless src cDNA clones. We conclude that the reduction of src mRNA
       levels triggered by the presence of frameshift mutations within the src
       gene occurs while it is associated with the nucleus. Our data also
       strongly suggest that this occurs at a step of RNA processing or
       transport independent of RNA splicing.
 DE    Animal  Cells, Cultured  Chick Embryo  Cytoplasm/METABOLISM  DNA
       Mutational Analysis  Frameshift Mutation  *Gene Expression Regulation,
       Viral  Genes, env  *Genes, src  In Vitro  Introns  Oncogene Protein
       pp60(v-src)/METABOLISM  Restriction Mapping  RNA, Messenger/*GENETICS
       RNA, Viral/GENETICS  Sarcoma Viruses, Avian/*GENETICS  Support, U.S.
       Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

