| Structural highlights
Function
THOC1_HUMAN Component of the THO subcomplex of the TREX complex. The TREX complex specifically associates with spliced mRNA and not with unspliced pre-mRNA. It 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. The recruitment occurs via an interaction between ALYREF/THOC4 and the cap-binding protein NCBP1. DDX39B functions as a bridge between ALYREF/THOC4 and the THO complex. The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production. The recruitment of the TREX complex to the intronless viral mRNA occurs via an interaction between KSHV ORF57 protein and ALYREF/THOC4.[1] [2] [3] [4] [5] [6] [7] [8] [9] Regulates transcriptional elongation of a subset of genes. Participates in an apoptotic pathway which is characterized by activation of caspase-6, increases in the expression of BAK1 and BCL2L1 and activation of NF-kappa-B. This pathway does not require p53/TP53, nor does the presence of p53/TP53 affect the efficiency of cell killing. Activates a G2/M cell cycle checkpoint prior to the onset of apoptosis. Apoptosis is inhibited by association with RB1.[10] [11] [12] [13] [14] [15] [16] [17] [18]
Publication Abstract from PubMed
Newly made mRNAs are processed and packaged into mature ribonucleoprotein complexes (mRNPs) and are recognized by the essential transcription-export complex (TREX) for nuclear export(1,2). However, the mechanisms of mRNP recognition and three-dimensional mRNP organization are poorly understood(3). Here we report cryo-electron microscopy and tomography structures of reconstituted and endogenous human mRNPs bound to the 2-MDa TREX complex. We show that mRNPs are recognized through multivalent interactions between the TREX subunit ALYREF and mRNP-bound exon junction complexes. Exon junction complexes can multimerize through ALYREF, which suggests a mechanism for mRNP organization. Endogenous mRNPs form compact globules that are coated by multiple TREX complexes. These results reveal how TREX may simultaneously recognize, compact and protect mRNAs to promote their packaging for nuclear export. The organization of mRNP globules provides a framework to understand how mRNP architecture facilitates mRNA biogenesis and export.
mRNA recognition and packaging by the human transcription-export complex.,Pacheco-Fiallos B, Vorlander MK, Riabov-Bassat D, Fin L, O'Reilly FJ, Ayala FI, Schellhaas U, Rappsilber J, Plaschka C Nature. 2023 Apr;616(7958):828-835. doi: 10.1038/s41586-023-05904-0. Epub 2023 , Apr 5. PMID:37020021[19]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Doostzadeh-Cizeron J, Evans R, Yin S, Goodrich DW. Apoptosis induced by the nuclear death domain protein p84N5 is inhibited by association with Rb protein. Mol Biol Cell. 1999 Oct;10(10):3251-61. PMID:10512864
- ↑ Doostzadeh-Cizeron J, Yin S, Goodrich DW. Apoptosis induced by the nuclear death domain protein p84N5 is associated with caspase-6 and NF-kappa B activation. J Biol Chem. 2000 Aug 18;275(33):25336-41. PMID:10840029 doi:http://dx.doi.org/10.1074/jbc.M000793200
- ↑ Doostzadeh-Cizeron J, Terry NH, Goodrich DW. The nuclear death domain protein p84N5 activates a G2/M cell cycle checkpoint prior to the onset of apoptosis. J Biol Chem. 2001 Jan 12;276(2):1127-32. PMID:11050087 doi:http://dx.doi.org/10.1074/jbc.M006944200
- ↑ Strasser K, Masuda S, Mason P, Pfannstiel J, Oppizzi M, Rodriguez-Navarro S, Rondon AG, Aguilera A, Struhl K, Reed R, Hurt E. TREX is a conserved complex coupling transcription with messenger RNA export. Nature. 2002 May 16;417(6886):304-8. Epub 2002 Apr 28. PMID:11979277 doi:http://dx.doi.org/10.1038/nature746
- ↑ Guo S, Hakimi MA, Baillat D, Chen X, Farber MJ, Klein-Szanto AJ, Cooch NS, Godwin AK, Shiekhattar R. Linking transcriptional elongation and messenger RNA export to metastatic breast cancers. Cancer Res. 2005 Apr 15;65(8):3011-6. PMID:15833825 doi:http://dx.doi.org/10.1158/0008-5472.CAN-04-3624
- ↑ Masuda S, Das R, Cheng H, Hurt E, Dorman N, Reed R. Recruitment of the human TREX complex to mRNA during splicing. Genes Dev. 2005 Jul 1;19(13):1512-7. PMID:15998806 doi:http://dx.doi.org/10.1101/gad.1302205
- ↑ Li Y, Wang X, Zhang X, Goodrich DW. Human hHpr1/p84/Thoc1 regulates transcriptional elongation and physically links RNA polymerase II and RNA processing factors. Mol Cell Biol. 2005 May;25(10):4023-33. PMID:15870275 doi:http://dx.doi.org/10.1128/MCB.25.10.4023-4033.2005
- ↑ Cheng H, Dufu K, Lee CS, Hsu JL, Dias A, Reed R. Human mRNA export machinery recruited to the 5' end of mRNA. Cell. 2006 Dec 29;127(7):1389-400. PMID:17190602 doi:http://dx.doi.org/10.1016/j.cell.2006.10.044
- ↑ Boyne JR, Colgan KJ, Whitehouse A. Recruitment of the complete hTREX complex is required for Kaposi's sarcoma-associated herpesvirus intronless mRNA nuclear export and virus replication. PLoS Pathog. 2008 Oct;4(10):e1000194. doi: 10.1371/journal.ppat.1000194. Epub, 2008 Oct 31. PMID:18974867 doi:http://dx.doi.org/10.1371/journal.ppat.1000194
- ↑ Doostzadeh-Cizeron J, Evans R, Yin S, Goodrich DW. Apoptosis induced by the nuclear death domain protein p84N5 is inhibited by association with Rb protein. Mol Biol Cell. 1999 Oct;10(10):3251-61. PMID:10512864
- ↑ Doostzadeh-Cizeron J, Yin S, Goodrich DW. Apoptosis induced by the nuclear death domain protein p84N5 is associated with caspase-6 and NF-kappa B activation. J Biol Chem. 2000 Aug 18;275(33):25336-41. PMID:10840029 doi:http://dx.doi.org/10.1074/jbc.M000793200
- ↑ Doostzadeh-Cizeron J, Terry NH, Goodrich DW. The nuclear death domain protein p84N5 activates a G2/M cell cycle checkpoint prior to the onset of apoptosis. J Biol Chem. 2001 Jan 12;276(2):1127-32. PMID:11050087 doi:http://dx.doi.org/10.1074/jbc.M006944200
- ↑ Strasser K, Masuda S, Mason P, Pfannstiel J, Oppizzi M, Rodriguez-Navarro S, Rondon AG, Aguilera A, Struhl K, Reed R, Hurt E. TREX is a conserved complex coupling transcription with messenger RNA export. Nature. 2002 May 16;417(6886):304-8. Epub 2002 Apr 28. PMID:11979277 doi:http://dx.doi.org/10.1038/nature746
- ↑ Guo S, Hakimi MA, Baillat D, Chen X, Farber MJ, Klein-Szanto AJ, Cooch NS, Godwin AK, Shiekhattar R. Linking transcriptional elongation and messenger RNA export to metastatic breast cancers. Cancer Res. 2005 Apr 15;65(8):3011-6. PMID:15833825 doi:http://dx.doi.org/10.1158/0008-5472.CAN-04-3624
- ↑ Masuda S, Das R, Cheng H, Hurt E, Dorman N, Reed R. Recruitment of the human TREX complex to mRNA during splicing. Genes Dev. 2005 Jul 1;19(13):1512-7. PMID:15998806 doi:http://dx.doi.org/10.1101/gad.1302205
- ↑ Li Y, Wang X, Zhang X, Goodrich DW. Human hHpr1/p84/Thoc1 regulates transcriptional elongation and physically links RNA polymerase II and RNA processing factors. Mol Cell Biol. 2005 May;25(10):4023-33. PMID:15870275 doi:http://dx.doi.org/10.1128/MCB.25.10.4023-4033.2005
- ↑ Cheng H, Dufu K, Lee CS, Hsu JL, Dias A, Reed R. Human mRNA export machinery recruited to the 5' end of mRNA. Cell. 2006 Dec 29;127(7):1389-400. PMID:17190602 doi:http://dx.doi.org/10.1016/j.cell.2006.10.044
- ↑ Boyne JR, Colgan KJ, Whitehouse A. Recruitment of the complete hTREX complex is required for Kaposi's sarcoma-associated herpesvirus intronless mRNA nuclear export and virus replication. PLoS Pathog. 2008 Oct;4(10):e1000194. doi: 10.1371/journal.ppat.1000194. Epub, 2008 Oct 31. PMID:18974867 doi:http://dx.doi.org/10.1371/journal.ppat.1000194
- ↑ Pacheco-Fiallos B, Vorländer MK, Riabov-Bassat D, Fin L, O'Reilly FJ, Ayala FI, Schellhaas U, Rappsilber J, Plaschka C. mRNA recognition and packaging by the human transcription-export complex. Nature. 2023 Apr;616(7958):828-835. PMID:37020021 doi:10.1038/s41586-023-05904-0
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