The new nucleoporin

Abstract

Transcriptional regulation is a complex process that requires the integrated action of many multi-protein complexes. The way in which a living cell coordinates the action of these complexes in time and space is still poorly understood. Recent work has shown that nuclear pores, well known for their role in 3′ processing and export of transcripts, also participate in the control of transcriptional initiation. We have recently begun to explore how nuclear pores interface with the well-described machinery that regulates initiation. This work led to the discovery that specific nucleoporins are required for binding of the repressor protein Mig1 to its site in target promoters. Nuclear pores are therefore involved in repressing, as well as activating, transcription. Here we discuss in detail the main models explaining our result and consider what each implies about the roles that nuclear pores play in the regulation of gene expression.

Nuclear Transport Deficits in Tau-Related Neurodegenerative Diseases

“…Another concept for a potential indirect interaction of tau with Nups is based on a study by Toda et al ( 141 ): Nup153 associates with the transcription factor Sox2 to regulate the neural fate of neural progenitor cells ( 141 ), whereby Nup153 binding to both the 5′ and the 3′ ends of genes enables a bimodal gene regulation. Other Nups also play a role in transcription regulation ( 128 , 142 , 143 ). Even though the interaction of tau with Nup153 has not been investigated, disease-associated binding of tau to Nups that play a role for transcription could induce tau-mediated gene alterations in neurodegenerative diseases.…”

Functional Genomics Evidence Unearths New Moonlighting Roles of Outer Ring Coat Nucleoporins

“…The Y-shaped Nup84/Nup107-160 subcomplex (Y-complex) forms the outer ring scaffold, is evolutionarily conserved, and is composed of certain key proteins referred to as outer ring coat nucleoporins (Y-Nups – 9 in vertebrates and 7 in yeast) 1 2 , with common structural features yet elusive sequence similarities 3 4 . While the functional capacities of coat nucleoporins are primarily connected with the nuclear pore and, in fact, despite their key role in maintaining the integrity of the outer ring, there is growing evidence for their involvement in other processes 5 6 , including mitotic spindle assembly 7 and transcription regulation 8 . Few other nucleoporins bind directly to the outer rings, rendering detection of their interacting partners experimentally highly challenging 1 .…”