RNA biogenesis is a highly coordinated and fundamental biological process that regulates the synthesis, processing, modification, maturation, transport and turnover of cellular RNA molecules. The coordinated production of wide range of RNAs and other non-coding RNAs is essential for maintaining gene expression, protein synthesis and cellular homeostasis. Ribosome quality control (RQC) provides an important protective mechanism by detecting defective or stalled ribosomes, resolving ribosome collisions, and eliminating abnormal nascent proteins and dysfunctional ribosomal components. RQC surveys incomplete nascent polypeptides produced by interrupted translation. Several protein players in RQC sense large ribosomal subunits obstructed with nascent chains and then promote nascent-chain proteolysis. Defects in RNA biogenesis and RNA-processing pathways have been increasingly associated with human diseases. Abnormal RNA splicing, RNA modification, RNA transport and RNA degradation are also implicated in diseases of CNS and cancers. The present review summarizes the RNA biogenesis, mechanisms through which RNA dysregulation contributes to human disease, using representative disease examples by providing background to basic concepts. We discuss individual category of diseases using representative diseases and the underlying genetic and cellular mechanisms. The application of ribosome biosynthesis in drug design against viral and antibiotic resistance and their applications in clinical medicine highlights their growing importance and roles in disease biology.
