| Structural highlights
Function
SPT5_YEAST The SPT4-SPT5 complex mediates both activation and inhibition of transcription elongation, and plays a role in pre-mRNA processing. This complex seems to be important for the stability of the RNA polymerase II elongation machinery on the chromatin template but not for the inherent ability of this machinery to translocate down the gene.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
The eukaryotic Spt4-Spt5 heterodimer forms a higher-order complex with RNA polymerase II (and I) to regulate transcription elongation. Extensive genetic and functional data have revealed diverse roles of Spt4-Spt5 in coupling elongation with chromatin modification and RNA processing pathways. Mechanistic understanding of the diverse functions of Spt4-Spt5 is hampered by challenges in resolving the distribution of functions amongst its structural domains including the five KOW domains in Spt5 and a lack of their high-resolution structures. We present high-resolution crystallographic results demonstrating that distinct structures are formed by the first through third KOW domains (KOW1-Linker1 and KOW2-KOW3) of yeast Spt5. The structure reveals that KOW1-Linker1 (K1L1) displays a positively charged patch (PCP) on its surface, which binds nucleic acids in vitro as shown in biochemical assays and is important for in vivo function as shown in growth assays. Furthermore, assays in yeast show that the PCP carries a function that partially overlaps that of Spt4. A synthesis of our results with previous evidence suggests a model in which Spt4 and the K1L1 domain of Spt5 form functionally overlapping interactions with nucleic acids upstream of the transcription bubble, and this mechanism may endow robustness to processes associated with transcription elongation.
Structures and functions of the multiple KOW domains of transcription elongation factor Spt5.,Meyer PA, Li S, Zhang M, Yamada K, Takagi Y, Hartzog GA, Fu J Mol Cell Biol. 2015 Jul 27. pii: MCB.00520-15. PMID:26217010[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rondon AG, Garcia-Rubio M, Gonzalez-Barrera S, Aguilera A. Molecular evidence for a positive role of Spt4 in transcription elongation. EMBO J. 2003 Feb 3;22(3):612-20. PMID:12554661 doi:http://dx.doi.org/10.1093/emboj/cdg047
- ↑ Lindstrom DL, Squazzo SL, Muster N, Burckin TA, Wachter KC, Emigh CA, McCleery JA, Yates JR 3rd, Hartzog GA. Dual roles for Spt5 in pre-mRNA processing and transcription elongation revealed by identification of Spt5-associated proteins. Mol Cell Biol. 2003 Feb;23(4):1368-78. PMID:12556496
- ↑ Mason PB, Struhl K. Distinction and relationship between elongation rate and processivity of RNA polymerase II in vivo. Mol Cell. 2005 Mar 18;17(6):831-40. PMID:15780939 doi:http://dx.doi.org/S1097-2765(05)01116-0
- ↑ Xiao Y, Yang YH, Burckin TA, Shiue L, Hartzog GA, Segal MR. Analysis of a splice array experiment elucidates roles of chromatin elongation factor Spt4-5 in splicing. PLoS Comput Biol. 2005 Sep;1(4):e39. Epub 2005 Sep 16. PMID:16172632 doi:http://dx.doi.org/10.1371/journal.pcbi.0010039
- ↑ Hartzog GA, Wada T, Handa H, Winston F. Evidence that Spt4, Spt5, and Spt6 control transcription elongation by RNA polymerase II in Saccharomyces cerevisiae. Genes Dev. 1998 Feb 1;12(3):357-69. PMID:9450930
- ↑ Meyer PA, Li S, Zhang M, Yamada K, Takagi Y, Hartzog GA, Fu J. Structures and functions of the multiple KOW domains of transcription elongation factor Spt5. Mol Cell Biol. 2015 Jul 27. pii: MCB.00520-15. PMID:26217010 doi:http://dx.doi.org/10.1128/MCB.00520-15
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