Aly/REF export factor, also known as THO complex subunit 4 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
that in humans is encoded by the ''ALYREF''
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
The ALYREF
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
encodes Aly/REF export factor (ALY; THO complex subunit 4, Tho4; RNA and export factor binding protein 1, Refbp1), a ubiquitously expressed
nuclear protein A nuclear protein is a protein found in the cell nucleus
The cell nucleus (pl. nuclei; from Latin or , meaning ''kernel'' or ''seed'') is a membrane-bound organelle found in eukaryotic cells. Eukaryotic cells usually have a single nucleus, b ...
that functions as a
molecular chaperone
In molecular biology, molecular chaperones are proteins that assist the conformational folding or unfolding of large proteins or macromolecular protein complexes. There are a number of classes of molecular chaperones, all of which function to as ...
and export adapter involved in nuclear export of spliced and unspliced
mRNA
In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of synthesizing a protein.
mRNA is created during the ...
. 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.
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