Structures and functions of the multiple KOW domains of transcription elongation factor Spt5

Peter A. Meyer, Sheng Li, Mincheng Zhang, Kentaro Yamada, Yuichiro Takagi, Grant A. Hartzog, Jianhua Fu

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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. A mechanistic understanding of the diverse functions of Spt4-Spt5 is hampered by challenges in resolving the distribution of functions among 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 [K1L1] and KOW2-KOW3) of Saccharomyces cerevisiae Spt5. The structure reveals that 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 have shown that the PCP has a function that partially overlaps that of Spt4. 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 confer robustness on processes associated with transcription elongation.

Original languageEnglish
Pages (from-to)3354-3369
Number of pages16
JournalMolecular and Cellular Biology
Volume35
Issue number19
DOIs
StatePublished - 2015

Fingerprint

Peptide Elongation Factors
Nucleic Acids
Transcription Factors
RNA Polymerase I
RNA Polymerase II
Chromatin
Saccharomyces cerevisiae
Yeasts
RNA
Growth
In Vitro Techniques

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Structures and functions of the multiple KOW domains of transcription elongation factor Spt5. / Meyer, Peter A.; Li, Sheng; Zhang, Mincheng; Yamada, Kentaro; Takagi, Yuichiro; Hartzog, Grant A.; Fu, Jianhua.

In: Molecular and Cellular Biology, Vol. 35, No. 19, 2015, p. 3354-3369.

Research output: Contribution to journalArticle

Meyer, Peter A. ; Li, Sheng ; Zhang, Mincheng ; Yamada, Kentaro ; Takagi, Yuichiro ; Hartzog, Grant A. ; Fu, Jianhua. / Structures and functions of the multiple KOW domains of transcription elongation factor Spt5. In: Molecular and Cellular Biology. 2015 ; Vol. 35, No. 19. pp. 3354-3369.
@article{c9af6664bf08495f80384eecef65de90,
title = "Structures and functions of the multiple KOW domains of transcription elongation factor Spt5",
abstract = "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. A mechanistic understanding of the diverse functions of Spt4-Spt5 is hampered by challenges in resolving the distribution of functions among 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 [K1L1] and KOW2-KOW3) of Saccharomyces cerevisiae Spt5. The structure reveals that 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 have shown that the PCP has a function that partially overlaps that of Spt4. 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 confer robustness on processes associated with transcription elongation.",
author = "Meyer, {Peter A.} and Sheng Li and Mincheng Zhang and Kentaro Yamada and Yuichiro Takagi and Hartzog, {Grant A.} and Jianhua Fu",
year = "2015",
doi = "10.1128/MCB.00520-15",
language = "English",
volume = "35",
pages = "3354--3369",
journal = "Molecular and Cellular Biology",
issn = "0270-7306",
publisher = "American Society for Microbiology",
number = "19",

}

TY - JOUR

T1 - Structures and functions of the multiple KOW domains of transcription elongation factor Spt5

AU - Meyer, Peter A.

AU - Li, Sheng

AU - Zhang, Mincheng

AU - Yamada, Kentaro

AU - Takagi, Yuichiro

AU - Hartzog, Grant A.

AU - Fu, Jianhua

PY - 2015

Y1 - 2015

N2 - 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. A mechanistic understanding of the diverse functions of Spt4-Spt5 is hampered by challenges in resolving the distribution of functions among 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 [K1L1] and KOW2-KOW3) of Saccharomyces cerevisiae Spt5. The structure reveals that 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 have shown that the PCP has a function that partially overlaps that of Spt4. 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 confer robustness on processes associated with transcription elongation.

AB - 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. A mechanistic understanding of the diverse functions of Spt4-Spt5 is hampered by challenges in resolving the distribution of functions among 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 [K1L1] and KOW2-KOW3) of Saccharomyces cerevisiae Spt5. The structure reveals that 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 have shown that the PCP has a function that partially overlaps that of Spt4. 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 confer robustness on processes associated with transcription elongation.

UR - http://www.scopus.com/inward/record.url?scp=84941126330&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941126330&partnerID=8YFLogxK

U2 - 10.1128/MCB.00520-15

DO - 10.1128/MCB.00520-15

M3 - Article

VL - 35

SP - 3354

EP - 3369

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

SN - 0270-7306

IS - 19

ER -