4l1p

Structural highlights

Function

[RTF1_HUMAN] Component of the PAF1 complex (PAF1C) which has multiple functions during transcription by RNA polymerase II and is implicated in regulation of development and maintenance of embryonic stem cell pluripotency. PAF1C associates with RNA polymerase II through interaction with POLR2A CTD non-phosphorylated and 'Ser-2'- and 'Ser-5'-phosphorylated forms and is involved in transcriptional elongation, acting both indepentently and synergistically with TCEA1 and in cooperation with the DSIF complex and HTATSF1. PAF1C is required for transcription of Hox and Wnt target genes. PAF1C is involved in hematopoiesis and stimulates transcriptional activity of MLL1; it promotes leukemogenesis though association with MLL-rearranged oncoproteins, such as MLL-MLLT3/AF9 and MLL-MLLT1/ENL. PAF1C is involved in histone modifications such as ubiquitination of histone H2B and methylation on histone H3 'Lys-4' (H3K4me3). PAF1C recruits the RNF20/40 E3 ubiquitin-protein ligase complex and the E2 enzyme UBE2A or UBE2B to chromatin which mediate monoubiquitination of 'Lys-120' of histone H2B (H2BK120ub1); UB2A/B-mediated H2B ubiquitination is proposed to be coupled to transcription. PAF1C is involved in mRNA 3' end formation probably through association with cleavage and poly(A) factors. In case of infection by influenza A strain H3N2, PAF1C associates with viral NS1 protein, thereby regulating gene transcription. Binds single-stranded DNA. Required for maximal induction of heat-shock genes. Required for the trimethylation of histone H3 'Lys-4' (H3K4me3) on genes involved in stem cell pluripotency; this function is synergistic with CXXC1 indicative for an involvement of a SET1 complex (By similarity).^{[1] [2]}

References

1. ↑ Ding L, Paszkowski-Rogacz M, Nitzsche A, Slabicki MM, Heninger AK, de Vries I, Kittler R, Junqueira M, Shevchenko A, Schulz H, Hubner N, Doss MX, Sachinidis A, Hescheler J, Iacone R, Anastassiadis K, Stewart AF, Pisabarro MT, Caldarelli A, Poser I, Theis M, Buchholz F. A genome-scale RNAi screen for Oct4 modulators defines a role of the Paf1 complex for embryonic stem cell identity. Cell Stem Cell. 2009 May 8;4(5):403-15. doi: 10.1016/j.stem.2009.03.009. Epub, 2009 Apr 2. PMID:19345177 doi:10.1016/j.stem.2009.03.009
2. ↑ Kim J, Guermah M, Roeder RG. The human PAF1 complex acts in chromatin transcription elongation both independently and cooperatively with SII/TFIIS. Cell. 2010 Feb 19;140(4):491-503. doi: 10.1016/j.cell.2009.12.050. PMID:20178742 doi:10.1016/j.cell.2009.12.050
3. ↑ Wier AD, Mayekar MK, Heroux A, Arndt KM, Vandemark AP. Structural basis for Spt5-mediated recruitment of the Paf1 complex to chromatin. Proc Natl Acad Sci U S A. 2013 Oct 7. PMID:24101474 doi:http://dx.doi.org/10.1073/pnas.1314754110