THO complex subunit 4

UniProt Q86V81 Organism Homo sapiens Gene ALY, ALYREF, BEF, THOC4

Also known as: ALY, ALYREF, BEF, THOC4

Function

Functions as an mRNA export adapter; component of the transcription/export (TREX) complex which is thought to couple mRNA transcription, processing and nuclear export, and specifically associates with spliced mRNA and not with unspliced pre-mRNA. TREX is recruited to spliced mRNAs by a transcription-independent mechanism, binds to mRNA upstream of the exon-junction complex (EJC) and is recruited in a splicing- and cap-dependent manner to a region near the 5' end of the mRNA where it functions in mRNA export to the cytoplasm via the TAP/NXF1 pathway. Involved in the nuclear export of intronless mRNA; proposed to be recruited to intronless mRNA by ATP-bound DDX39B. Plays a key role in mRNP recognition and mRNA packaging by bridging the mRNP-bound EJC and the TREX core complex. TREX recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1. Required for TREX complex assembly and for linking DDX39B to the cap-binding complex (CBC). Binds mRNA which is thought to be transferred to the NXF1-NXT1 heterodimer for export (TAP/NXF1 pathway). In conjunction with THOC5 functions in NXF1-NXT1 mediated nuclear export of HSP70 mRNA; both proteins enhance the RNA binding activity of NXF1 and are required for NXF1 localization to the nuclear rim. Involved in mRNA export of C5-methylcytosine (m5C)-containing mRNAs: specifically recognizes and binds m5C mRNAs and mediates their nucleo-cytoplasmic shuttling. Acts as a chaperone and promotes the dimerization of transcription factors containing basic leucine zipper (bZIP) domains and thereby promotes transcriptional activation. Involved in transcription elongation and genome stability.

Classification

Family (Pfam): PF13865 FoP_duplication, PF00076 RRM_1
InterPro: ALYREF_mRNA_export, FoP_C, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf, RRM_dom
Functional cluster: Translation Initiation/Elongation GTPases

Experimental structures · PDB · 4

3ULH X-ray 2.54A
7ZNJ EM 2.40A
7ZNK EM 3.90A
8R7L EM 4.12A

A predicted model is available from AlphaFold.

Gene Ontology · 19

Neighborhood · nearest proteins

Nearest neighbours of THO complex subunit 4: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Spliceosome RNA helicase DDX39B 11 shared papers
Aly/REF export factor 2 3 shared papers
Nuclear RNA export factor 1 10 shared papers
mRNA export factor 2 shared papers
THO complex subunit 5 9 shared papers
THO complex subunit 1 9 shared papers
THO complex subunit 2 8 shared papers
THO complex subunit 3 7 shared papers
RNA cytosine C(5)-methyltransferase NSUN2 1 shared papers
RNA-binding protein 8A 7 shared papers
THO complex subunit 7 6 shared papers
THO complex subunit 6 5 shared papers

Literature · 48 cited papers

mRNA recognition and packaging by the human transcription-export complex. Nature · 2023
Structural-functional interactions of NS1-BP protein with the splicing and mRNA export machineries for viral and host gene expression. Proc. Natl. Acad. Sci. U.S.A. · 2018
5-methylcytosine promotes mRNA export - NSUN2 as the methyltransferase and ALYREF as an m5C reader. Cell Res. · 2017
N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
Luzp4 defines a new mRNA export pathway in cancer cells. Nucleic Acids Res. · 2015
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
Immunoaffinity enrichment and mass spectrometry analysis of protein methylation. Mol. Cell. Proteomics · 2014
Mapping interactions between mRNA export factors in living cells. PLoS ONE · 2013
Aly and THO are required for assembly of the human TREX complex and association of TREX components with the spliced mRNA. Nucleic Acids Res. · 2013
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
TREX exposes the RNA-binding domain of Nxf1 to enable mRNA export. Nat. Commun. · 2012
N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
… and 36 more in the literature graph

A document in the lmmol reference corpus — open public data (UniProt, GO, PDB, the literature graph) rendered as a single cross-linked page. Hover any link to preview its target.