The yeast Saccharomyces cerevisiae likes to be in control, especially when it comes to gene expression. We already knew that transcription, splicing, messenger RNA export, mRNA stability, mRNA translation and post-translational modification are regulated processes. Tollervey and colleagues now report in Cell that degradation of unspliced pre-mRNAs occurs in the nucleus in a regulated manner, providing yet another regulatory mechanism for gene expression.

Using several mutants defective in mRNA processing, Tollervey and co-workers found that unspliced pre-mRNAs are degraded in the nucleus in a 3′ to 5′ direction by a large protein complex containing several exoribonucleases (the exosome), or in a 5′ to 3′ direction by the exonuclease Rat1p . This is, in fact, similar to what is known to happen in the cytosol, where mRNAs are degraded either 3′ to 5′ by the exosome or 5′ to 3′ by the cytosolic exonuclease Xrn1p. But contrary to what happens in the cytosol, exosome-mediated degradation is predominant in the nucleus.

Nuclear degradation of pre-mRNA seems to compete with splicing. It is increased in the presence of glucose — yeast's favourite food — indicating that it is a physiological regulatory pathway for gene expression. The 3′ to 5′ Rat1p-dependent pathway is probably inhibited by the cap structure of the pre-mRNA, providing another level of control.

Degradation of inaccurately spliced pre-mRNAs has also been observed in mammalian cells, and there again, the activity seems to be nuclear. An obvious experiment will be to test whether homologues of the genes identified in yeast have the same function in mammalian cells.