Intron or no intron: a matter for nuclear pore complexes

Abstract

Nuclear pore complexes (NPCs) have been shown to regulate distinct steps of the gene expression process, from transcription to mRNA export. In particular, mRNAs expressed from intron-containing genes are surveyed by a specific NPC-dependent quality control pathway ensuring that unspliced mRNAs are retained within the nucleus. In this Extra View, we summarize the different approaches that have been developed to evaluate the contribution of various NPC components to the expression of intron-containing genes. We further present the mechanistic models that could account for pre-mRNA retention at the nuclear side of NPCs. Finally, we discuss the possibility that other stages of intron-containing gene expression could be regulated by nuclear pores, in particular through the regulation of mRNA biogenesis factors by the NPC-associated SUMO protease Ulp1.

Keywords: SUMO-protease Ulp1; THO/TREX complex; mRNA export; mRNA quality control; mRNA transcription; nuclear pore complexes; sumoylation.

Figure 1.

Models accounting for nuclear pore-associated quality control prior to mRNA export (A). In the “selection” model, the nuclear basket only docks export-competent mRNPs by interacting with dedicated mRNP components, while faulty mRNPs, unable to interact with the NPC, are retained in the nucleus. Proteins possibly marking export-competent particles are depicted. (B) In the “retention” model, the nuclear basket would interact with proteins specifically present on unprocessed mRNPs, preventing their export through the pore. Putative signals of incomplete processing are represented. (C) Both models can be reconciled if physical interactions of different strengths are engaged between the nuclear basket and distinct kinds of mRNPs. Dynamic interactions with export-competent mRNPs would favor their export while stronger interactions with faulty mRNPs would durably tether them at NPCs, either favoring the completion of processing/packaging events or triggering degradation by the NPC-associated endonuclease Swt1.

Figure 2.

Possible functions of the Nup84 complex and Ulp1 in gene transcription. The sumoylated components of the transcription machinery which could mediate the roles of the Nup84 complex and Ulp1 in gene expression are represented. While Ulp1 was shown to target both Ssn6 and the THO complex for desumoylation, its activity toward Rap1 and Sir2 has not been investigated. The different boxes illustrate the positive role of sumoylated Rap1 in transcriptional activation (left), as well as the function of sumoylated Ssn6 and desumoylated Sir2 in transcriptional repression at glucose-repressed genes and subtelomeres, respectively (center). THO complex sumoylation differentially affects the expression of intron-containing and intronless reporters, most likely at the transcriptional elongation stage (right). RNAP II, RNA polymerase II.