Nuclear noncoding RNA surveillance: is the end in sight?

Nuclear noncoding RNA (ncRNA) surveillance pathways play key roles in shaping the steady-state transcriptomes of eukaryotic cells. Defective and unneeded ncRNAs are primarily degraded by exoribonucleases that rely on protein cofactors to identify these RNAs. Recent studies have begun to elucidate both the mechanisms by which these cofactors recognize aberrant RNAs and the features that mark RNAs for degradation. One crucial RNA determinant is the presence of an accessible end; in addition, the failure of aberrant RNAs to fold into compact structures and assemble with specific binding proteins probably also contributes to their recognition and subsequent degradation. To date, ncRNA surveillance has been most extensively studied in budding yeast. However, mammalian cells possess nucleases and cofactors that have no known yeast counterparts, indicating that RNA surveillance pathways may be more complex in metazoans. Importantly, there is evidence that the failure of ncRNA surveillance pathways contributes to human disease.