RNA quality control in the nucleus: the Angels' share of RNA

Biological processes are not exempt from errors and RNA production is not an exception to this rule. Errors can arise stochastically or be genetically fixed and systematically appear in the biochemical or cellular phenotype. In any case, quality control mechanisms are essential to minimize the potentially toxic effects of faulty RNA production or processing. Although many RNA molecules express their functional potential in the cytoplasm, as messengers, adaptors or operators of gene expression pathways, a large share of quality control occurs in the nucleus. This is likely because the early timing of occurrence and the subcellular partition make the control more efficient, at least as long as the defects can be detected ahead of the cytoplasmic phase of the RNA life cycle. One crucial point in discussing RNA quality control resides in its definition. A stringent take would imply the existence of specific mechanisms to recognize the error and the consequent repair or elimination of the faulty molecule. One example in the RNA field could be the recognition of a premature stop codon by the nonsense-mediated decay pathway, discussed elsewhere in this issue. A more relaxed view posits that the thermodynamic or kinetic aftermath of a mistake (e.g. a blockage or a delay in processing) by itself constitutes the recognition event, which triggers downstream quality control. Because whether inappropriate molecules are specifically recognized remains unclear in many cases, we will adopt the more relaxed definition of RNA quality control. RNA repair remains episodic and the degradative elimination of crippled molecules appears to be the rule. Therefore we will briefly describe the actors of RNA degradation in the nucleus. Detailed analyses of the mechanism of action of these enzymes can be found in several excellent and recent reviews, including in this issue. Finally, we will restrict our analysis to the yeast model, which is used in the majority of RNA quality control studies, but examples exist in the literature indicating that many of the principles of RNA quality control described in yeast also apply to other eukaryotes. This article is part of a Special Issue entitled: RNA Decay mechanisms.