Chemistry of Life

Molecular genetics, biochemistry

nonstop decay

Nonstop decay is mRNA turnover mechanism that has none of the properties of nonsense-mediated decay (NMD), or of normal mRNA turnover in the cell. The non-stop decay mechanism releases ribosomes that have stalled at the 3' end of a mRNA and stimulates the exosome to rapidly degrade the transcript.

The exosome is a large complex of riboexonucleases found in the nucleus and the cytoplasm that is required for the processing of all types of RNA molecules, except tRNAs. The riboexonuclease Rrp6p is a component of the nuclear exosome, and is a hydrolytic enzyme that degrades RNA molecules in a 3'-5' direction. Rrp6p plays a role in rRNA processing, ribosome biogenesis, and in a nuclear mRNA degradation pathway that destroys slowly, or improperly processed mRNAs.

One percent of genes in both humans and yeast produce mRNAs containing specific sequences that would trigger degradation of the RNA by nonstop decay. The fact that these sequences have been conserved suggests that these nonstop transcripts, and the proteins that they encode, may be important to normal development. Nonstop mRNA transcripts could be important for production of shortened proteins needed at specific stages of development. Later in development, when these truncated proteins are no longer necessary, their mRNA could easily be destroyed by nonstop decay.

Many of the most powerful biological regulators of cell growth and proliferation are encoded by unstable mRNAs, which are targeted for rapid degradation by the cell. The loss of rapid degradation of these growth-promoting mRNAs can result in oncogenic transformation of the cell. Targeted degradation of proto-oncogene mRNAs and short-lived cytokines is controlled both by an AU-rich element (ARE) located in the 3' noncoding region, and by several proteins that bind the ARE sequence. Activation of the ARE for mRNA decay involves cotranslation of the mRNA by ribosomes, and employs the ubiquitin-proteasome pathway.[s]

Researchers Discover New Mechanism That Targets And Destroys Abnormal RNA: Adapted: "Messenger RNA molecules are the genetic templates for synthesis of proteins. In constructing proteins, the mRNA template is transcribed from DNA genes and transported to the ribosomes – the cell's protein "factories" that are large complexes of protein and RNA. Given the importance of mRNA as an information-carrying molecule, the machinery that regulates mRNA levels and destroys faulty mRNA is critical in ensuring that errors in the genetic code are not passed on to proteins.

"Nonstop decay is mRNA turnover mechanism that has none of the properties of nonsense-mediated decay (NMD), or of normal mRNA turnover in the cell. Nonstop decay shares none of the enzymes required for nonsense-mediated decay. A multi-enzyme complex called the exosome is important for nonstop decay, this is the site where binding of a specific adapter protein called Ski7p binds. Ski7p recognizes these ribosomes holding nonstop mRNAs, and recruits the exosome to degrade the defective messages.

One percent of genes in both humans and yeast produce mRNAs containing specific sequences that would trigger degradation of the RNA by nonstop decay. Nonstop mRNA transcripts might be important in enabling production of shortened proteins that are needed at specific stages of development. At later stages of development, when these truncated proteins are no longer needed, their mRNA could easily be destroyed by nonstop decay."

The original news release can be found here.

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. . . transcription begun 10/06/06