Transcription-Export complex in neurodevelopmental disorders

The genomic information is insulated in the nucleus of all eukaryotic cells. Error-free transcription needs to be followed by an efficient export of the messenger RNAs (mRNA) to facilitate the regulated synthesis of proteins for carrying out cellular functions. The functionally conserved Transcription-Export (TREX) complex is a key player in mediating mRNA export from the nucleus to the cytoplasm, along with RNA processing steps including 3′-end processing, 5′ capping, transcriptional regulation, R-loop resolution, and splicing. TREX, a multifunctional complex, has important roles in stress response, mitotic progression, embryonic stem cell self-renewal and differentiation, and maintaining genome stability. Most of these processes are essential for the appropriate development and function of the brain. Consistent with this notion, partial loss of function variants in the TREX components THOC2, THOC6, and DDX39B were implicated in neurodevelopmental disorders. Furthermore, a growing body of evidence also highlighted the involvement of defective nucleocytoplasmic RNA transport in the development of neurodegenerative diseases. Overall, the TREX complex is emerging as a crucial player in neurological diseases, making it a critical target for both diagnosis and therapeutic intervention.