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Spliceosome RNA helicase DDX39B

Definition:

Involved in nuclear export of spliced and unspliced mRNA. Assembling component of the 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/NFX1 pathway. May undergo several rounds of ATP hydrolysis during assembly of TREX to drive subsequent loading of components such as ALYREF/THOC and CHTOP onto mRNA. Also associates with pre-mRNA independent of ALYREF/THOC4 and the THO complex. Involved in the nuclear export of intronless mRNA; the ATP-bound form is proposed to recruit export adapter ALYREF/THOC4 to intronless mRNA; its ATPase activity is cooperatively stimulated by RNA and ALYREF/THOC4 and ATP hydrolysis is thought to trigger the dissociation from RNA to allow the association of ALYREF/THOC4 and the NXF1-NXT1 heterodimer. Involved in transcription elongation and genome stability.; Splice factor that is required for the first ATP-dependent step in spliceosome assembly and for the interaction of U2 snRNP with the branchpoint. Has both RNA-stimulated ATP binding/hydrolysis activity and ATP-dependent RNA unwinding activity. Even with the stimulation of RNA, the ATPase activity is weak. Can only hydrolyze ATP but not other NTPs. The RNA stimulation of ATPase activity does not have a strong preference for the sequence and length of the RNA. However, ssRNA stimulates the ATPase activity much more strongly than dsRNA. Can unwind 5' or 3' overhangs or blunt end RNA duplexes in vitro. The ATPase and helicase activities are not influenced by U2AF2; the effect of ALYREF/THOC4 is reported conflictingly with [PubMed:23299939] reporting a stimulatory effect.; (Microbial infection) The TREX complex is essential for the export of Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs and infectious virus production.

References:

[1]. Hong Cheng, et al. Human mRNA export machinery recruited to the 5' end of mRNA. Cell. 2006 Dec 29;127(7):1389-400. [Content Brief]

[2]. Chung-Te Chang, et al. Chtop is a component of the dynamic TREX mRNA export complex. EMBO J. 2013 Feb 6;32(3):473-86. [Content Brief]

[3]. Seiji Masuda, et al. Recruitment of the human TREX complex to mRNA during splicing. Genes Dev. 2005 Jul 1;19(13):1512-7. [Content Brief]

[4]. M L Luo, et al. Pre-mRNA splicing and mRNA export linked by direct interactions between UAP56 and Aly. Nature. 2001 Oct 11;413(6856):644-7. [Content Brief]

[5]. Shanchun Guo, et al. Linking transcriptional elongation and messenger RNA export to metastatic breast cancers. Cancer Res. 2005 Apr 15;65(8):3011-6. [Content Brief]

[6]. Hang Shi, et al. Crystal structure of the human ATP-dependent splicing and export factor UAP56. Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17628-33. [Content Brief]

[7]. J Fleckner, et al. U2AF65 recruits a novel human DEAD box protein required for the U2 snRNP-branchpoint interaction. Genes Dev. 1997 Jul 15;11(14):1864-72. [Content Brief]

[8]. Ichiro Taniguchi, et al. ATP-dependent recruitment of export factor Aly/REF onto intronless mRNAs by RNA helicase UAP56. Mol Cell Biol. 2008 Jan;28(2):601-8. [Content Brief]

[9]. María S Domínguez-Sánchez, et al. Genome instability and transcription elongation impairment in human cells depleted of THO/TREX. PLoS Genet. 2011 Dec;7(12):e1002386. [Content Brief]

[10]. Binkai Chi, et al. 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 Jan;41(2):1294-306. [Content Brief]

[11]. Kobina Dufu, et al. ATP is required for interactions between UAP56 and two conserved mRNA export proteins, Aly and CIP29, to assemble the TREX complex. Genes Dev. 2010 Sep 15;24(18):2043-53. [Content Brief]

[12]. Jingping Shen, et al. Biochemical characterization of the ATPase and helicase activity of UAP56, an essential pre-mRNA splicing and mRNA export factor. J Biol Chem. 2007 Aug 3;282(31):22544-50. [Content Brief]

[13]. James R Boyne, et al. 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. [Content Brief]

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