Quality control of mRNP biogenesis: Networking at the transcription site

•The mechanisms of quality control of mRNA biogenesis monitor every step in gene expression.•The quality control is coupled to the exosome and to the 5′–3′ exoribonucleases XRN2 and DXO.•Defective transcripts can be exported to the cytoplasm and become NMD substrates.•The quality control feeds back to transcription and represses the synthesis of defective mRNAs.•An interaction network integrates multiple mRNA decay systems with the transcription machinery. Eukaryotic cells carry out quality control (QC) over the processes of RNA biogenesis to inactivate or eliminate defective transcripts, and to avoid their production. In the case of protein-coding transcripts, the quality controls can sense defects in the assembly of mRNA–protein complexes, in the processing of the precursor mRNAs, and in the sequence of open reading frames. Different types of defect are monitored by different specialized mechanisms. Some of them involve dedicated factors whose function is to identify faulty molecules and target them for degradation. Others are the result of a more subtle balance in the kinetics of opposing activities in the mRNA biogenesis pathway. One way or another, all such mechanisms hinder the expression of the defective mRNAs through processes as diverse as rapid degradation, nuclear retention and transcriptional silencing. Three major degradation systems are responsible for the destruction of the defective transcripts: the exosome, the 5′–3′ exoribonucleases, and the nonsense-mediated mRNA decay (NMD) machinery. This review summarizes recent findings on the cotranscriptional quality control of mRNA biogenesis, and speculates that a protein–protein interaction network integrates multiple mRNA degradation systems with the transcription machinery.