6zv4

Structural highlights

Disease

TCEA1_HUMAN Note=A chromosomal aberration involving TCEA1 may be a cause of salivary gland pleiomorphic adenomas (PA) [181030]. Pleiomorphic adenomas are the most common benign epithelial tumors of the salivary gland. Translocation t(3;8)(p21;q12) with PLAG1.

Function

TCEA1_HUMAN Necessary for efficient RNA polymerase II transcription elongation past template-encoded arresting sites. The arresting sites in DNA have the property of trapping a certain fraction of elongating RNA polymerases that pass through, resulting in locked ternary complexes. Cleavage of the nascent transcript by S-II allows the resumption of elongation from the new 3'-terminus.IWS1_HUMAN Transcription factor which plays a key role in defining the composition of the RNA polymerase II (RNAPII) elongation complex and in modulating the production of mature mRNA transcripts. Acts as an assembly factor to recruit various factors to the RNAPII elongation complex and is recruited to the complex via binding to the transcription elongation factor SUPT6H bound to the C-terminal domain (CTD) of the RNAPII subunit RPB1 (POLR2A). The SUPT6H:IWS1:CTD complex recruits mRNA export factors (ALYREF/THOC4, EXOSC10) as well as histone modifying enzymes (such as SETD2) to ensure proper mRNA splicing, efficient mRNA export and elongation-coupled H3K36 methylation, a signature chromatin mark of active transcription.^{[1] [2] [3]}

References

1. ↑ Liu Z, Zhou Z, Chen G, Bao S. A putative transcriptional elongation factor hIws1 is essential for mammalian cell proliferation. Biochem Biophys Res Commun. 2007 Feb 2;353(1):47-53. doi:, 10.1016/j.bbrc.2006.11.133. Epub 2006 Dec 5. PMID:17184735 doi:http://dx.doi.org/10.1016/j.bbrc.2006.11.133
2. ↑ Yoh SM, Cho H, Pickle L, Evans RM, Jones KA. The Spt6 SH2 domain binds Ser2-P RNAPII to direct Iws1-dependent mRNA splicing and export. Genes Dev. 2007 Jan 15;21(2):160-74. doi: 10.1101/gad.1503107. PMID:17234882 doi:http://dx.doi.org/10.1101/gad.1503107
3. ↑ Yoh SM, Lucas JS, Jones KA. The Iws1:Spt6:CTD complex controls cotranscriptional mRNA biosynthesis and HYPB/Setd2-mediated histone H3K36 methylation. Genes Dev. 2008 Dec 15;22(24):3422-34. doi: 10.1101/gad.1720008. PMID:19141475 doi:http://dx.doi.org/10.1101/gad.1720008
4. ↑ Cermakova K, Demeulemeester J, Lux V, Nedomova M, Goldman SR, Smith EA, Srb P, Hexnerova R, Fabry M, Madlikova M, Horejsi M, De Rijck J, Debyser Z, Adelman K, Hodges HC, Veverka V. A ubiquitous disordered protein interaction module orchestrates transcription elongation. Science. 2021 Nov 26;374(6571):1113-1121. doi: 10.1126/science.abe2913. Epub 2021, Nov 25. PMID:34822292 doi:http://dx.doi.org/10.1126/science.abe2913