Nucleus and gene expression The interplay of transcriptional and post-transcriptional mechanisms that regulate gene expression Editorial overview Elisa Izaurralde and David L Spector Current Opinion in Cell Biology 2004, 16:219–222 0955-0674/$ – see front matter ß 2004 Elsevier Ltd. All rights reserved. DOI 10.1016/j.ceb.2004.04.005 Elisa Izaurralde European Molecular Biology Laboratory, Gene Expression Program, Meyerhofstrasse 1. D-69117 Heidelberg, Germany Elisa Izaurralde is a Research Group leader at the European Molecular Biology Laboratory. Her laboratory studies mechanisms of post- transcriptional regulation of gene expression with particular emphasis on the nuclear export of messenger RNAs to the cytoplasm and mRNA turnover. David L Spector Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724 USA David L Spector is a Professor at Cold Spring Harbor Laboratory. His laboratory studies nuclear organization and the dynamics of gene expression in living cells. Abbreviations EJC exon–exon junction complex mRNP messenger ribonucleoprotein particle NPC nuclear pore complex RNAi RNA interference RNAP RNA polymerase During the past years post-transcriptional mechanisms have emerged as central pathways in the regulation of gene expression. In particular, the discovery of RNA-mediated gene silencing processes (RNA interference or RNAi) has revolutionized the field of gene expression both conceptually and experimentally. RNAi silences gene expression in a sequence-specific manner in response to the presence of double-stranded RNA. The identi- fication of the key molecular players in this process has been followed by an increased appreciation that they function as part of large protein assemblies that act at the interface of transcriptional and post-transcriptional regulatory circuits (see the review by Murchison and Hannon). Indeed, RNAi and related processes have been shown to regulate heterochromatin formation resulting in transcriptional silencing or to act at the post-transcriptional level, either by targeting mRNAs for degradation or by inhibiting translation. Consequently, the gene silencing apparatus intersects the chromatin remo- deling machineries in the nucleus, and the translation and mRNA turnover machineries in the cytoplasm. The first review in this issue by Murchison and Hannon covers recent progress on RNAi, as this topic has ramifications in all steps of gene expression. This is followed by four reviews, which examine the following topics: the regulation of heterochromatin by histone modifications and RNAi, the maintenance of chromatin states by the polycomb group of proteins, the inactivation of one X chromosome in female mammals (a specialized epigenetic mechanism regulating the expression of an entire chromosome), and how spatial localization in the nucleus can influence gene expression. The next reviews cover events in mRNA biogenesis. Starting from the regulation of transcription, we move into aspects related to the co- transcriptional assembly and processing of messenger ribonucleoprotein particles (mRNPs) and their export to the cytoplasm through nuclear pore complexes. The next group of three reviews focuses on cytoplasmic mRNP metabolism including mRNA turnover, the transport of mRNPs to specific cytoplasmic locations, and localized translation. The next two reviews focus on the dynamics of the nuclear pore complex during the cell cycle and how defects in nuclear lamin A are correlated with hereditary human diseases. The issue concludes with a review on the cellular response to DNA damage and the maintenance of genome stability, and a commentary on the www.sciencedirect.com Current Opinion in Cell Biology 2004, 16:219–222