Review Article

Transcriptional Elongation and mRNA Export Are Coregulated Processes

Figure 1

Coordination of different steps in transcription initiation, mRNP biogenesis, and export facilitates gene expression. (a) Active genes are recruited to the nuclear periphery through the factors involved in both transcription and mRNPs export. In the transcription activation process, there is an interaction via SAGA and Sus1 between the promoter and the NPC tethering the genes to the nuclear periphery. Mlp1 (myosin-like protein 1) is also involved in the recruitment of the GAL1 gene to the NPC upon transcription activation. (b) The TREX complex is recruited to nascent mRNA in the early steps of transcription elongation although there are differences between yeast and metazoan when considering genome complexity. Whereas TREX is recruited cotranscriptionally in yeast, it is recruited by spliceosome components in metazoan likely due to the highest percentage of intron-containing genes [14, 15]. Adaptor proteins (Yra1, Nab2, and Npl3) recognise RNA when the transcript is competent for export to the cytoplasm, and they recruit it to export factors such as Mex67-Mtr2. This recruitment to export factors is crucial for generating mature mRNP. (c) Once the mRNP is properly formed and assembled, it is assumed that the export is facilitated by a close location to the NPC. TREX-2 (also known as THSC) mediates the location of active genes to the NPC through a binding to both the NPC nuclear face and the SAGA complex. The crystal structure of Sus1 and Cdc31 [16], bound to a central region of Sac3, forms a conserved interaction platform that promotes NPC association and mRNA export to provide a scaffold that integrates the interaction between protein complexes and facilitates the coupling of transcription and mRNA export [17]. Thp1 and Sac3 mediate the docking of mRNP at the NPC through its interaction with Mex67-Mtr2 and nucleoporins. mRNPs share the 5′-to-3′ polarity of movement through the NPC. Although the exact manner of how the transport of mRNPs takes place has not been precisely described, the most widely accepted hypothesis is that mRNPs are pulled through the NPC via ATP hydrolysis by the shuttling ATPase Dbp5 (hDbp5). Dbp5/Rat8 binds to the cytoplasmic filaments of the NPC by interacting with two nucleoporins (Nup159 and Nup 42) and Gle1. Gle1, together with its cofactor IP6, stimulates the ATPase activity of Dbp5. Once inside the cytoplasm, mRNA is released, and mRNP proteins are removed by entering a new export cycle.
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