Premature translation termination mediates triosephosphate isomerase mRNA degradation.

AUTOR(ES)

Daar, I O

RESUMO

We characterized an anemia-inducing mutation in the human gene for triosephosphate isomerase (TPI) that resulted in the production of prematurely terminated protein and mRNA with a reduced cytoplasmic half-life. The mutation converted a CGA arginine codon to a TGA nonsense codon and generated a protein of 188 amino acids, instead of the usual 248 amino acids. To determine how mRNA primary structure and translation influence mRNA stability, in vitro-mutagenized TPI alleles were introduced into cultured L cells and analyzed for their effect on TPI RNA metabolism. Results indicated that mRNA stability is decreased by all nonsense and frameshift mutations. To determine the relative contribution of the changes in mRNA structure and translation to the altered half-life, the effects of individual mutations were compared with the effects of second-site reversions that restored translation termination to normal. All mutations that resulted in premature translation termination reduced the mRNA half-life solely or mainly by altering the length of the mRNA that was translated. The only mutation that altered translation termination and that reduced the mRNA half-life mainly by affecting the mRNA structure was an insertion that shifted termination to a position downstream of the normal stop codon.

Documentos Relacionados

• Vaccinia virus induces cellular mRNA degradation.
• The nonamer UUAUUUAUU is the key AU-rich sequence motif that mediates mRNA degradation.
• Poly(A) tail shortening is the translation-dependent step in c-myc mRNA degradation.
• Effect of premature termination of translation on mRNA stability depends on the site of ribosome release.
• Histone mRNA concentrations are regulated at the level of transcription and mRNA degradation.