Substrate specificity of the exonuclease activity that degrades H4 histone mRNA.

A Mutation in the tRNA Nucleotidyltransferase Gene Promotes Stabilization of mRNAs in Saccharomyces cerevisiae

“…This conclusion is drawn from observations that the mRNAstabilizing effects of cycloheximide occur very rapidly (16, 30a), and additional experiments with yeast cells which show that (i) mRNA instability elements have been localized to coding regions (12,14,15,17,26,31), (ii) the function of the coding region instability element from the M4Tao mRNA is dependent on ribosome progression up to or through the element (26), and (iii) destabilization of mRNAs by premature translational termination requires downstream sequences that appear to act as translational reinitiation sites (30,31). In addition to these observations for yeast cells, experiments with mammalian cells demonstrate that (i) the nucleases capable of degrading mammalian mRNAs in vitro are associated with polysomes (29,34), (ii) the exonuclease activity that degrades histone mRNA in a cell-free mRNA decay system is not affected by treating the cells with cycloheximide (28), (iii) sequences in the coding regions of the 3-tubulin, c-myc, and c-fos genes are important for rapid or regulated turnover of their transcripts (5,36,39), and (iv) the regulation of tubulin, histone, and c-nyc mRNA turnover requires ongoing protein synthesis (9,10,36). Collectively, these results suggest an important role for the ribosome (or one of its subunits) in the decay process.…”

A cell-free extract from yeast cells for studying mRNA turnover

“…In this respect the recent development of mammalian cell-free mRNA decay systems (16)(17)(18) constitutes an important step forward since such systems considerably facilitate the identification, purification and characterization of such factors. By means of such a system, for instance, Ross and coworkers have documented the involvement of a 3'-5' exoribonuclease in the degradation of histone mRNA (19)(20)(21) and provided evidence for feed-back control of this degradation by histones (22). Similar systems have led to the identification, among others, of a nucleoprotein factor destabilizing c-myc mRNA by binding to its AU-rich sequence (23,24), a nuclease activity tightly associated with mammalian mRNP particles, that interacts in a highly specific fashion with individual mRNAs (25), an estrogen-induced ribonuclease activity in Xenopus laevis liver cells involved in albumin mRNA degradation (26) and an activity induced upon herpes simplex viral infection that destabilizes host mRNA (27).…”