The SAGA - TREX-2 Interaction

During transcription, nascent mRNA is associated with the mRNA-binding proteins that are involved in processing and export of the mRNA particle. TREX-2 interacts with transcription co-activator,  SAGA (see Fig. 1), and nuclear pore complex (NPCs) (Cabal et al., 2006), in order to couple gene transcription with mRNA export. This coupling provides a suitable molecular environment for gene expression regulation and produces export-competent mRNPs thus increases the success and the rate of mRNA export (Brickner, D.G. et al., 2007). It has been shown that disconnection between transcription and mRNA export results in several human genetic disorders (Nousiainen, H. O. et al., 2008; Zhang, M. et al., 2007).

SAGA

SAGA stands for Spt–Ada–Gcn5–acetyltransferase, a chromatin-modifying transcriptional co-activator complex, comprising of 21 proteins. There are two inherent catalytic activities:

• Histone acetyltransferase activity (HAT)
• Histone H2B deubiquitylation activity (DUB)

The correct functioning of the two activities convert the compact and hence inactive chromatin to open and active chromatin.

TREX-2

TREX-2 is also a multiprotein complex. It is highly conserved, thus demonstrating its importance in organisms. TREX-2 is anchored on the inner face of the NPC by association of Sac3 with the Thp1, Cdc31 and Sus1 subunits (see Fig. 2). The determination of the structure of TREX-2 revealed that the central region of Sac3 (the CID domain) adopts a long alpha-helix conformation, wrapped by one Cdc31 and two Sus1 molecules. This structure suggests the role of TREX-2 in coupling transcription and mRNA export and gene gating in Saccharomyces cerevisiae.

Interplay Between SAGA and TREX-2

Fig. 1  Gene transcription is activated by SAGA via its binding to the promoter. During transcription elongation, one of its subunit, Sus1, is recruited to the coding regions via phosphorylated RNAPII CTD in order to couple transcription initiation and elongation. TREX-2 is also vital for transcription elongation.

The common component between SAGA and TREX-2 is Sus1, which coordinates the activity of both machineries (see Fig. 2).

Fig. 2  TREX-2 binds to both the nucleoporins on the NPC nuclear surface and the SAGA complex, physically attaching the activated gene locus to the nuclear pore. Thus, TREX-2 directly promotes mRNA export. Nuclear basket proteins facilitate gene anchoring stabilization. Phosphorylated RNAPII shown here is able to recruit export factors (e.g. Sus1, Mex67 and Yra1) to interact with the NPC-bound TREX-2 complex.

- Written by Xiao Xiao Han