Nuclear pore complexes and regulation of gene expression

Abstract

Nuclear pore complexes (NPCs), are large multiprotein channels that penetrate the nuclear envelope connecting the nucleus to the cytoplasm. Accumulating evidence shows that besides their main role in regulating the exchange of molecules between these two compartments, NPCs and their components also play important transport-independent roles, including gene expression regulation, chromatin organization, DNA repair, RNA processing and quality control, and cell cycle control. Here, we will describe the recent findings about the role of these structures in the regulation of gene expression.

Figure 1. NPC-gene association in yeast

Upon activation several inducible yeast genes re-localize to nuclear pore complexes. Factors involved in NPC tethering include nucleoporins (Mlp1, Mlp2, Nup1, Nup2, Nup42, Nup60, Nup100, Nup116, Nup157, Gle2), cis-DNA elements or Gene Recruitment Sequences (GRS), transcription factors (TF) including Put3, Cbf1, Gcn4, Ste12, Gal4, Sfl1, chromatin modulators (SAGA, HDACs), transport export complexes TREX-2/THO-TREX (TREX) and Mediator.

Figure 2. Gene regulation by nucleoporins and NPCs in metazoans

In Drosophila and mammalian cells, several nucleoporins regulate gene expression inside the nucleus and independent of NPCs. Nup98, Nup62, Nup50, and Sec13 (NUP) have been shown to bind and regulate developmental and cell cycle genes. A soluble form of the transmembrane nucleoporin Pom121 (sPom121) binds many target genes together with Nup98. Nup98 also interacts with the histone-modifying complexes MBD-R2/NSL and Trx/MLL. MBD-R2/NSL is required for Nup98 recruitment to its target genes. Nup153 on the other hand recruits the polycomb complex PRC1 to gene promoters repressing the activity of developmental genes.