4ytk

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.