Disease relevance of SUPT5H

• This novel biochemical function of Spt5 is analogous to the function of NusG, an elongation factor found in Escherichia coli that enhances RNA polymerase stability on templates and shows sequence similarity to Spt5 [1].
• In this study, we analyze the domains of SPT5 that regulate transcriptional elongation in the presence of either DRB or the HIV-1 Tat protein [2].
• SPT4 and SPT5 are involved in both 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB)-mediated transcriptional inhibition and the activation of transcriptional elongation by the human immunodeficiency virus type 1 (HIV-1) Tat protein [2].

High impact information on SUPT5H

• Consistent with capping enzyme binding, TFIIH-phosphorylated CTD stimulated guanylylation, and this increase was not additive with hSPT5 [3].
• Methylation of SPT5 regulates its interaction with RNA polymerase II and transcriptional elongation properties [4].
• Specific arginine residues in SPT5 that are methylated by these enzymes were identified and demonstrated to be important in regulating its promoter association and subsequent effects on transcriptional elongation [4].
• These results suggest that methylation of SPT5 is an important posttranslational modification that is involved in regulating its transcriptional elongation properties in response to viral and cellular factors [4].
• These data suggest that Spt4p, Spt5p, and, potentially, other regulators of Pol I transcription elongation play important roles in coupling rRNA transcription to its processing and ribosome assembly [5].

Chemical compound and disease context of SUPT5H

• Flavopiridol, a potent P-TEFb kinase inhibitor, inhibits CTD phosphorylation, stable SPT5 binding, and histone methylation, suggesting that its potent antiviral activity is due to its ability to inhibit several critical and unique steps in HIV-1 transcription elongation [6].

Biological context of SUPT5H

• However, Spt5 plays an important role in late elongation by preventing the premature dissociation of RNA from the transcription complex at terminator sequences and reducing the amount of polymerase pausing at arrest sites, including bent DNA sequences [1].
• Furthermore, the SPT5 CTR1 domain is a substrate for P-TEFb phosphorylation [2].
• Modulating HIV-1 replication by RNA interference directed against human transcription elongation factor SPT5 [7].

Associations of SUPT5H with chemical compounds

• Phosphorylation of hSPT5 by P-TEFb occurred on threonine and serine residues in its carboxyl-terminal repeat domains [8].

Other interactions of SUPT5H

• SUPT5H maps to 19q13, near the ryanodine receptor [9].
• The Spt4, Spt5, and Spt6 proteins are conserved eukaryotic transcription-elongation factors [10].

References