Frameshift mutations in the v-src gene of avian sarcoma virus act in cis to specifically reduce v-src mRNA levels - PubMed (original) (raw)

Frameshift mutations in the v-src gene of avian sarcoma virus act in cis to specifically reduce v-src mRNA levels

S B Simpson et al. Mol Cell Biol. 1994 Mar.

Abstract

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.

PubMed Disclaimer

Cited by

Nuclear degradation of nonsense mutated beta-globin mRNA: a post-transcriptional mechanism to protect heterozygotes from severe clinical manifestations of beta-thalassemia?
Kugler W, Enssle J, Hentze MW, Kulozik AE. Kugler W, et al. Nucleic Acids Res. 1995 Feb 11;23(3):413-8. doi: 10.1093/nar/23.3.413. Nucleic Acids Res. 1995. PMID: 7885837 Free PMC article.
Identification and characterization of a sequence motif involved in nonsense-mediated mRNA decay.
Zhang S, Ruiz-Echevarria MJ, Quan Y, Peltz SW. Zhang S, et al. Mol Cell Biol. 1995 Apr;15(4):2231-44. doi: 10.1128/MCB.15.4.2231. Mol Cell Biol. 1995. PMID: 7891717 Free PMC article.
Unspliced Rous sarcoma virus genomic RNAs are translated and subjected to nonsense-mediated mRNA decay before packaging.
LeBlanc JJ, Beemon KL. LeBlanc JJ, et al. J Virol. 2004 May;78(10):5139-46. doi: 10.1128/jvi.78.10.5139-5146.2004. J Virol. 2004. PMID: 15113896 Free PMC article.
mRNA surveillance in eukaryotes: kinetic proofreading of proper translation termination as assessed by mRNP domain organization?
Hilleren P, Parker R. Hilleren P, et al. RNA. 1999 Jun;5(6):711-9. doi: 10.1017/s1355838299990519. RNA. 1999. PMID: 10376871 Free PMC article. Review.
Selective inhibition of splicing at the avian sarcoma virus src 3' splice site by direct-repeat posttranscriptional cis elements.
Guo W, Winistorfer SC, Stoltzfus CM. Guo W, et al. J Virol. 2000 Sep;74(18):8513-23. doi: 10.1128/jvi.74.18.8513-8523.2000. J Virol. 2000. PMID: 10954552 Free PMC article.

References

1. Virology. 1973 Apr;52(2):456-67 - PubMed
1. Genes Dev. 1993 Sep;7(9):1737-54 - PubMed
1. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5134-7 - PubMed
1. Cell. 1983 Mar;32(3):853-69 - PubMed
1. Proc Natl Acad Sci U S A. 1983 May;80(9):2519-23 - PubMed

Frameshift mutations in the v-src gene of avian sarcoma virus act in cis to specifically reduce v-src mRNA levels - PubMed (original) (raw)