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Beschreibung
Transcription elongation factor SPT5 (UniProt: O00267, also known as hSPT5, DRB sensitivity-inducing factor 160 kDa subunit, DSIF p160, DRB sensitivity-inducing factor large subunit, DSIF large subunit, Tat-co-transactivator 1 protein, Tat-CT1 protein) is encoded by the SUPT5H (also known as SPT5, SPT5H) gene (Gene ID: 6829) in human. SPT5 is a component of the DRB sensitivity-inducing factor complex (DSIF complex), which regulates mRNA processing and transcription elongation by RNA polymerase II. DSIF is a heterodimer of SPT4 and SPT5 that positively regulates mRNA capping by stimulating the mRNA guanylyltransferase activity of RNGTT/CAP1A. DSIF also acts cooperatively with the negative elongation factor complex (NELF complex) to enhance transcriptional pausing at sites proximal to the promoter. Transcriptional pausing can facilitate the assembly of an elongation competent RNA polymerase II complex. DSIF and NELF promote pausing by inhibition of the transcription elongation factor TFIIS/S-II, which binds to RNA polymerase II at transcription pause sites and stimulates the weak intrinsic nuclease activity of the enzyme. Cleavage of blocked transcripts by RNA polymerase II promotes the resumption of transcription from the new 3' terminus and may allow repeated attempts at transcription through natural pause sites. DSIF can also positively regulate transcriptional elongation and is required for the efficient activation of transcriptional elongation by the HIV-1 nuclear transcriptional activator, Tat. SPT5 can be methylated by PRMT1/HRMT1L2 and PRMT5/SKB1 and this methylation negatively regulates interaction with the positive transcription elongation factor (P-TEFb) and RNA polymerase II.
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