Disease relevance of SPT5

• Role of the human homolog of the yeast transcription factor SPT5 in HIV-1 Tat-activation [1].

High impact information on SPT5

• We find that Spt5 and Spt6 localize extensively with the phosphorylated, actively elongating form of Pol II, to transcriptionally active sites during salivary gland development and upon heat shock [2].
• In addition, we show that spt4, spt5, and spt6 mutants themselves have phenotypes suggesting defects in transcription elongation in vivo [3].
• Finally, we show that Spt4 and Spt5 are tightly associated in a complex that does not contain Spt6 [3].
• RNA polymerase II, TFIIS, Spt5, and, unexpectedly, the Paf1/Cdc73 complex, were found associated with open reading frames [4].
• Thirdly, we demonstrate that deletion of CHD1 suppresses a cold-sensitive spt5 mutation that is also suppressed by defects in the Paf1 complex and RNA pol II [5].

Biological context of SPT5

• SPT5, an essential gene important for normal transcription in Saccharomyces cerevisiae, encodes an acidic nuclear protein with a carboxy-terminal repeat [6].
• The SPT5 DNA sequence was determined; it predicted a 116-kDa protein with an extremely acidic amino terminus and a novel six-amino-acid repeat at the carboxy terminus (consensus = S-T/A-W-G-G-A/Q) [6].
• Absence of the Nhp6 proteins causes severe impairment in combination with mutations impairing the Swi-Snf chromatin-remodeling complex and the DSIF (Spt4 plus Spt5) elongation regulator, and sensitizes cells to 6-azauracil, characteristic of elongation effects [7].
• Previous studies suggest that Spt4p functions in a complex with Spt5p and Spt6p, and we determined that spt6-140 also causes missegregation of a chromosome fragment [8].
• The C-terminal domain of the 990-amino acid Schizosaccharomyces pombe Spt5 protein, composed of repeats of a nonapeptide motif (consensus sequence TPAWNSGSK), is necessary and sufficient for binding to the capping enzymes in vivo (in a two-hybrid assay) and in vitro [9].

Anatomical context of SPT5

• Our results suggest that the Spt4-Spt5 complex may help coordinate splicing with transcription under conditions that present kinetic challenges to spliceosome assembly or function [10].
• From HeLa cells we have purified a human homologue of Spt5p, Supt5hp, and show here that the protein is reversibly phosphorylated in mitosis [11].

Physical interactions of SPT5

• We find that Spt5 is essential for viability of S. pombe and that it interacts in vivo with S. pombe Spt4 via a central domain distinct from the Spt5 CTD [9].

Enzymatic interactions of SPT5

• SpCdk9/Pch1 phosphorylates of the carboxyl-terminal domain (CTD) of the S. pombe transcription elongation factor Spt5, which consists of 18 tandem repeats of a nonapeptide of consensus sequence 1TPAWNSGSK9 [12].

Other interactions of SPT5

• We have now analyzed interactions between SPT4, SPT5 and SPT6 [13].
• Finally, the results of coimmunoprecipitation experiments demonstrate that at least the SPT5 and SPT6 proteins interact physically [13].
• Mutations in the SPT5 gene of Saccharomyces cerevisiae were isolated previously as suppressors of delta insertion mutations at HIS4 and LYS2 [6].
• In addition, we independently isolated paf1 and leo1 mutations in an unbiased genetic screen for suppressors of a cold-sensitive spt5 mutation [14].
• In vivo evidence that defects in the transcriptional elongation factors RPB2, TFIIS, and SPT5 enhance upstream poly(A) site utilization [15].

Analytical, diagnostic and therapeutic context of SPT5

• By indirect immunofluorescence microscopy we showed that a bifunctional SPT5-beta-galactosidase protein was located in the yeast nucleus [6].
• Using a genomic approach to characterize the roles of Spt4-5 in splicing, we used splicing-sensitive DNA microarrays to identify specific sets of genes that are mis-spliced in ceg1, spt4, and spt5 mutants [10].
• Crosslinking and immunoprecipitation experiments show that Spt5 is present at uninduced heat shock gene promoters, and that upon heat shock, Spt5 and Spt6 associate with the 5' and 3' ends of heat shock genes [16].

References