THOC5
Description
The THOC5 (THO complex subunit 5) is a protein-coding gene located on chromosome 22.
THOC5, encoded by the THOC5 gene, is a protein involved in mRNA processing and export as part of the THO complex. THOC5 is conserved in higher eukaryotes, but its exact role remains unclear. It is phosphorylated by various kinases in response to extracellular stimuli like growth factors, cytokines, chemokines, and DNA damage reagents. THOC5 is a substrate for oncogenic tyrosine kinases, suggesting a potential role in cancer development. Knockout mouse studies highlight THOC5's essential role in maintaining stem cells and growth factor/cytokine-mediated differentiation and proliferation. THOC5 significantly influences the export of immediate-early genes induced by extracellular stimuli, despite minimal impact on overall mRNA export in steady-state conditions. This suggests its crucial role in 3' processing and/or export of genes activated by external signals.
THOC5 is a component of the THO subcomplex within the TREX complex, a protein complex involved in coupling mRNA transcription, processing, and export. It specifically associates with spliced mRNA, not unspliced pre-mRNA. TREX is recruited to spliced mRNAs independently of transcription, binds to mRNA upstream of the exon-junction complex (EJC), and is recruited to the 5' end of mRNA in a splicing- and cap-dependent manner. This complex facilitates mRNA export to the cytoplasm via the TAP/NFX1 pathway. THOC5, alongside ALYREF/THOC4, plays a role in NXF1-NXT1-mediated nuclear export of HSP70 mRNA. Together, they enhance NXF1's RNA binding activity and are necessary for NXF1 localization to the nuclear rim. THOC5 also contributes to transcription elongation, genome stability, and alternative polyadenylation site selection by recruiting CPSF6 to the 5' region of target genes, potentially bridging the TREX and CFIm complexes.
THOC5 is also known as C22orf19, Fmip, PK1.3, fSAP79.
