The art of unwinding: RNA helicases at the crossroads of cell biology and human disease

The centrality of RNA in the flow of information from the genome is the basis of the main dogma of cell biology. However, rules and roles governing RNA function have been dramatically expanded in the last decade with the discovery of pervasive transcription of eukaryotic genomes and also with the growing importance of the non-coding genomic output. RNA is an extremely plastic and versatile molecule, which carries out a myriad of functions ranging from enzymatic catalysis to scaffold of protein complexes. Folding of RNA molecules is a fast and dynamic process, essential for their biological functions, that often requires the presence of specialized molecular machinery. RNA helicases are a wide, ubiquitous and multifunctional family of proteins classically related, but not restricted, to the RNA folding function. RNA homeostasis is essential for the cell, and is ensured by the presence of RNA helicases. Nevertheless, RNA helicase functions are far to be restricted to the RNA folding problem. Selected members of this complex family are involved in many other functions such as regulation of gene expression by non-coding RNAs, detection of specific RNA molecules, sensing of small compounds or transduction of metabolic signals. This comprehensive review analyzes the functional roles of RNA helicases in several areas, with special emphasis in their roles in human disease and their relationships with the non-coding RNAs.