Multifunctional regulatory proteins that control gene expression in both the nucleus and the cytoplasm

The multistep pathway of eukaryotic gene expression involves a series of hi ghly regulated events in the nucleus and cytoplasm. In the nucleus, genes a re transcribed into pre-messenger RNAs which undergo a series of nuclear pr ocessing steps. Mature mRNAs are then transported to the cytoplasm, where t hey are translated into protein and degraded at a rate dictated by transcri pt- and cell-type-specific cues. Until recently, these individual nuclear a nd cytoplasmic events were thought to be primarily regulated by different R NA- and DNA-binding proteins that are localized either only in the nucleus or only the cytoplasm. Here, we describe multifunctional proteins that cont rol both nuclear and cytoplasmic steps of gene expression. One such class o f multifunctional proteins (e.g., Bicoid and Y-box proteins) regulates both transcription and translation whereas another class (e.g., Sex-lethal) reg ulates both nuclear RNA processing and translation. Other events controlled by multifunctional proteins include assembly of spliceosome components, sp liceosome recycling, RNA editing, cytoplasmic mRNA localization, and cytopl asmic RNA stability. The existence of multifunctional proteins may explain the paradoxical involvement of the nucleus in an RNA surveillance pathway ( nonsense-mediated decay) that detects cytoplasmic signals (premature termin ation codons). We speculate that shuttling multifunctional proteins serve t o efficiently link RNA metabolism in the cytoplasmic and nuclear compartmen ts. (C) 2001 John Wiley & Sons, Inc.