ALYREF
Description
The ALYREF (Aly/REF export factor) is a protein-coding gene located on chromosome 17.
ALY/REF export factor, also known as THO complex subunit 4 is a protein that in humans is encoded by the ALYREF gene. The ALYREF gene encodes Aly/REF export factor (ALY; THO complex subunit 4, Tho4; RNA and export factor binding protein 1, Refbp1), a ubiquitously expressed nuclear protein that functions as a molecular chaperone and export adapter involved in nuclear export of spliced and unspliced mRNA. The TRanscription-EXport (TREX) complex, a key player in mRNA export, includes the THO subcomplex, the RNA helicase UAP56, and the RNA-binding protein ALY. In yeast, TREX is recruited co-transcriptionally; in human cells it is recruited during a late step of splicing. The human TREX complex is recruited to a region near the 5' end of mRNA by interaction of ALY and THO with the nuclear cap-binding complex. As a chaperone, ALY promotes dimerization of transcription factors containing basic leucine zipper (bZIP) domains., thereby promoting transcriptional activation. ALY has key roles in 3'-end processing of polyadenylated mRNAs and in nuclear export of both polyadenylated and non-polyadenylated mRNAs. After mRNA binds to ALY, it is apparently transferred to the NXF1-NXT1 heterodimer for export (TAP/NFX1 pathway). The full-length ALY protein (Refbp1-I, 255 amino acids encoded by six exons) has a conserved RNA recognition motif (RRM; amino acids 105-182) flanked by alanine/arginine/glycine-rich sequences; an N-terminal region (amino acids 16-37) is sufficient for RNA binding and interaction with the NXF1-NXT1 heterodimer.
ALYREF, also known as THO complex subunit 4, is involved in the nuclear export of both spliced and unspliced mRNA. It acts as a molecular chaperone and export adapter, binding to mRNA and facilitating its transfer to the NXF1-NXT1 heterodimer for export. ALYREF is a component of the TREX complex, which couples mRNA transcription, processing, and nuclear export, specifically associating with spliced mRNA. TREX is recruited to spliced mRNAs via a splicing- and cap-dependent mechanism and interacts with the cap-binding protein NCBP1, enabling mRNA export to the cytoplasm. ALYREF is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and viral production. ALYREF plays a role in TREX complex assembly and links DDX39B to the cap-binding complex (CBC). In conjunction with THOC5, it functions in NXF1-NXT1 mediated nuclear export of HSP70 mRNA, enhancing NXF1 RNA binding and nuclear rim localization. ALYREF is also involved in the nuclear export of intronless mRNA, potentially recruited by ATP-bound DDX39B. Additionally, ALYREF contributes to transcription elongation, genome stability, and the export of mRNAs containing C5-methylcytosine (m5C), specifically recognizing and binding to these mRNAs and mediating their nucleo-cytoplasmic shuttling.
ALYREF is also known as ALY, ALY/REF, BEF, REF, THOC4.
