LAUSR

RNA turnover is an integral part of cellular RNA homeostasis and gene expression regulation. Whereas the cytoplasmic control of protein-coding mRNA is often the focus of study, we discuss here the less appreciated role of nuclear RNA decay systems in controlling RNA polymerase II (RNAPII)-derived transcripts. Historically, nuclear RNA degradation was found to be essential for the functionalization of transcripts through their proper maturation. Later, it was discovered to also be an important caretaker of nuclear hygiene by removing aberrant and unwanted transcripts. Recent years have now seen a set of new protein complexes handling a variety of new substrates, revealing functions beyond RNA processing and the decay of non-functional transcripts. This includes an active contribution of nuclear RNA metabolism to the overall cellular control of RNA levels, with mechanistic implications during cellular transitions.RNA is controlled at various stages of transcription and processing to achieve appropriate gene regulation. Whereas much research has focused on the cytoplasmic control of RNA levels, this Review discusses our emerging appreciation of the importance of nuclear RNA regulation, including the molecular machinery involved in nuclear RNA decay, how functional RNAs bypass degradation and roles for nuclear RNA decay in physiology and disease.