SAGA and a novel Drosophila export complex anchor efficient transcription and mRNA export to NPC

Abstract

SAGA/TFTC-type multiprotein complexes play important roles in the regulation of transcription. We have investigated the importance of the nuclear positioning of a gene, its transcription and the consequent export of the nascent mRNA. We show that E(y)2 is a subunit of the SAGA/TFTCtype histone acetyl transferase complex in Drosophila and that E(y)2 concentrates at the nuclear periphery. We demonstrate an interaction between E(y)2 and the nuclear pore complex (NPC) and show that SAGA/TFTC also contacts the NPC at the nuclear periphery. E(y)2 forms also a complex with X-linked male sterile 2 (Xmas-2) to regulate mRNA transport both in normal conditions and after heat shock. Importantly, E(y)2 and Xmas-2 knockdown decreases the contact between the heat-shock protein 70 (hsp70) gene loci and the nuclear envelope before and after activation and interferes with transcription. Thus, E(y)2 and Xmas-2 together with SAGA/TFTC function in the anchoring of a subset of transcription sites to the NPCs to achieve efficient transcription and mRNA export.

A role for DNA sequence in controlling the spatial organization of the genome

“…The hsp70 gene cluster in Drosophila physically interacts with the NPC and localizes to the nuclear periphery. 23 In mouse tissue culture cells, some genes that are derepressed by treatment with the histone deacetylase inhibitor TSA also relocalize to the nuclear periphery and physically interact with the NPC. 24 Furthermore, in male flies, the entire X chromosome localizes at the nuclear periphery and interacts with the NPC.…”

“…39 The hsp70 gene cluster localizes at the nuclear periphery, interacts with the NPC and expression of these genes depends on proteins that interact with the NPC. 23 The localization of the male X chromosome in Drosophila to the nuclear periphery involves interaction with the NPC and this is important for interaction with MSL dosage compensation factors, suggesting a correlation between peripheral localization and increased transcription. 25 Thus many genes require localization to the nuclear periphery for full activation.…”

Nonreplicative functions of the origin recognition complex

“…However, recently we have shown, that the ORC complex interacts with coding mRNAs and participates in mRNA export in D. melanogaster . Moreover, ORC interacts with TREX-2, the complex of general mRNA nuclear export [17,108]. Besides that, we have shown an interaction between the ORC subunits and the Nxf1 protein, the mRNA transport receptor [17].…”

Sem1

“…Further, only Sem1, but not other components of the RP, is genetically linked to essential components of the mRNA export pathway (Mex67, Mtr2, subset of gene loci from the nuclear interior to the nuclear periphery upon their activation. [11][12][13][14][15] …”