| 1997 |
RTF1 (Rtf1) was identified as a nuclear protein in yeast that regulates TBP DNA-binding properties and TATA site selection; loss-of-function and missense alleles alter transcription initiation, and the rtf1 null suppresses effects of a Ty delta insertion in the HIS4 promoter, indicating Rtf1 modulates TBP-dependent promoter activity in vivo. |
Genetic suppressor screen, indirect immunofluorescence localization, transcription start-site mapping |
Molecular and cellular biology |
Medium |
9234706
|
| 2000 |
Rtf1 functions as a transcription elongation factor in S. cerevisiae; rtf1Δ is sensitive to 6-azauracil and mycophenolic acid (elongation-defect markers), and synthetic lethal interactions were found with elongation factors SPT4, SPT5, SPT16, PPR2, CTD kinase CTK1, CTD phosphatase FCP1, and Srb/Mediator component SRB5. |
Synthetic lethal screen, 6-azauracil/mycophenolic acid sensitivity assays, genetic epistasis |
Genetics |
Medium |
11014804
|
| 2002 |
Rtf1 is a component of the Paf1/RNA Pol II complex in S. cerevisiae, associated with Paf1, Cdc73, Ctr9, Leo1, and Pol II but not with the Srb-mediator; deletion of RTF1 suppresses many paf1Δ phenotypes including growth defects and reduced CLN1 expression. |
Tandem affinity purification, mass spectrometry, genetic double-mutant analysis |
Molecular and cellular biology |
High |
11884586
|
| 2003 |
Rtf1 is required for global histone H2B ubiquitination at K123 in yeast, and this activity underlies its role in promoting H3-K4 and H3-K79 methylation (but not H3-K36 methylation); Rtf1 also promotes recruitment of Set1 (H3-K4 methylase) to the 5′ region of active genes and is important for telomeric silencing. |
Chromatin immunoprecipitation, histone modification western blots, genetic deletion analysis |
The Journal of biological chemistry |
High |
12876293
|
| 2008 |
The Plus3 domain of human RTF1 adopts an NMR structure with a β-stranded subdomain resembling PAZ/Tudor domains and can bind single-stranded DNA in vitro via residues on the rim of the β-sheet, suggesting a role in transcription elongation. |
NMR structure determination, in vitro DNA binding assays |
Structure |
Medium |
18184592
|
| 2008 |
S. pombe Rtf1 (replication termination factor) mediates site-specific replication termination at the RTS1 polar barrier through two chimeric myb/SANT domains; one domain interacts with RTS1 repeated motifs and the enhancer region, and the C-terminal tail mediates self-interaction required for polarity of termination. NOTE: This paper describes the S. pombe replication-termination Rtf1, which is a distinct protein from the transcriptional elongation Rtf1/PAF1C subunit. |
Domain mapping, DNA binding assays, point mutagenesis, dominant phenotype analysis |
Genetics |
Medium |
18723894
|
| 2011 |
Single amino acid substitutions in the conserved histone modification domain (HMD) of yeast Rtf1 abolish H2B ubiquitylation and impair H3 methylation; HMD mutations also disrupt snoRNA 3′-end formation, revealing a role for Rtf1-dependent H2BK123 ubiquitylation in noncoding RNA termination. |
Site-directed mutagenesis, histone modification assays, 3′-end processing assays, genetic analysis |
Genetics |
High |
21441211
|
| 2012 |
A 90-amino acid histone modification domain (HMD) of Rtf1, when expressed as the sole Rtf1 source in yeast, is sufficient to promote H3-K4, H3-K79 methylation, and H2B-K123 ubiquitylation independently of other Paf1C subunits and without requiring a DNA-tethering fusion, and the HMDs from other species function in yeast. |
Domain truncation/expression in rtf1Δ cells, chromatin immunoprecipitation, histone modification western blots |
Proceedings of the National Academy of Sciences of the United States of America |
High |
22699496
|
| 2013 |
A highly conserved domain of yeast Rtf1 directly interacts with the C-terminal repeat domain (CTR) of Spt5 to recruit the Paf1 complex to active chromatin; mutations disrupting this interaction or deletion of the Spt5 CTR release Paf1C from chromatin, and the Rtf1 Spt5-interacting domain alone can associate with active genes in a Spt5-CTR-dependent manner. |
Co-immunoprecipitation, in vitro binding assays, chromatin immunoprecipitation, mutagenesis |
Molecular and cellular biology |
High |
23775116
|
| 2013 |
In S. pombe, Cdk9 phosphorylation of Spt5 creates a direct binding site for Prf1/Rtf1; Prf1 and PAF complex are biochemically separate in cell extracts and exert opposing effects on the RNAPII elongation complex, defining two distinct Cdk9-dependent pathways with opposing effects on elongation and H2B monoubiquitylation. |
Co-immunoprecipitation, genetic epistasis, biochemical fractionation, phosphorylation-dependent binding assays |
PLoS genetics |
High |
24385927
|
| 2015 |
Human RTF1 functions as a transcription elongation factor independently of the PAF1 complex; it requires a 'Rtf1 coactivator' activity (distinct from PAF1C or DSIF) for transcriptional activation in vitro, the Plus3 domain is critical for this function, and human RTF1 and PAF1C regulate distinct gene subsets with PAF1C recruited to genes independently of RTF1. |
In vitro transcription assays, RNA-seq, chromatin immunoprecipitation, mutational analysis |
Molecular and cellular biology |
High |
26217014
|
| 2016 |
The HMD of yeast Paf1C subunit Rtf1 directly interacts with the ubiquitin-conjugating enzyme Rad6 to stimulate H2B ubiquitylation; the crystal structure of the Rtf1 HMD was solved, a conserved Rad6-interaction surface was identified by site-specific in vivo crosslinking, and HMD-dependent stimulation of H2Bub was demonstrated in a transcription-free reconstituted in vitro system. |
Crystal structure determination, in vitro H2B ubiquitylation assay (transcription-free), site-specific in vivo crosslinking, ChIP-exo |
Molecular cell |
High |
27840029
|
| 2020 |
Cryo-EM structure of the complete porcine/human Pol II elongation complex (EC*) containing RTF1 reveals that the RTF1 Plus3 domain contacts Pol II subunit RPB12 and the phosphorylated C-terminal region of DSIF subunit SPT5; RTF1 extends four α-helices along the Pol II protrusion/RPB10 to the funnel, and a C-terminal 'latch' reaching the bridge helix is required for RTF1's strong stimulation of Pol II elongation, suggesting allosteric activation of translocation. |
Cryo-EM structure determination, in vitro Pol II elongation assays, mutagenesis |
Nature structural & molecular biology |
High |
32541898
|
| 2020 |
In S. pombe, the Plus3 domain of Prf1/Rtf1 and phospho-Spt5 act in parallel (not linearly) to promote Prf1 function; an alternate Plus3 interface overlapping the pSpt5-binding site can interact with single-stranded nucleic acid or with the PAF complex in vitro, and the Prf1 C-terminal region also acts in parallel with pSpt5. |
Genetic epistasis, in vitro binding assays (Plus3 domain vs. ssDNA, PAF), mutagenesis |
Molecular and cellular biology |
Medium |
32366382
|
| 2023 |
The primary contact surface for the Rtf1 HMD on Rad6 is the highly conserved N-terminal helix of Rad6; separation-of-function mutations in RAD6 that impair the Rad6-HMD interaction selectively block H2B-K123 ubiquitylation without affecting other Rad6 functions, and transcriptome profiles of these mutants closely resemble those of H2B ubiquitylation-site mutants. |
In vitro crosslinking/mass spectrometry, in vivo protein crosslinking, genetic separation-of-function mutagenesis, RNA-seq |
Proceedings of the National Academy of Sciences of the United States of America |
High |
37216505
|
| 2023 |
Rtf1 is essential for cardiogenesis in zebrafish and mouse; loss of Rtf1 arrests cardiac progenitors in an immature state, the Plus3 domain (mediating Spt5 interaction) is required for cardiac progenitor formation, ChIP-seq shows reduced RNAPII occupancy at the TSS of cardiac genes in rtf1 morphants (reflecting reduced pausing), and pharmacological inhibition of CDK9-dependent pause release restores cardiomyocyte formation. |
Morpholino knockdown, genetic knockout (zebrafish/mouse), ChIP-seq, CDK9 inhibitor rescue |
eLife |
High |
41537425
|
| 2023 |
Rtf1 ablation in neonatal and adult mouse cardiomyocytes causes sarcomere breakdown, myofibril disorganization, disrupted cell-cell junctions, fibrosis, and dilated cardiomyopathy-like systolic dysfunction, demonstrating continuous requirement for Rtf1 in maintaining cardiac structural gene expression. |
Cardiomyocyte-specific knockout (mouse), neonatal knockdown, histology, echocardiography, gene expression profiling |
Journal of cardiovascular development and disease |
Medium |
37233188
|
| 2025 |
An N-terminal region of Rtf1 directly interacts with the CHCT domain of the nucleosome remodeler Chd1; disrupting this interaction causes Chd1 accumulation at gene 5′ ends, increased cryptic transcription, altered nucleosome positioning, and shifted histone modification profiles. The interaction is conserved: mouse RTF1 interacts with CHCT domains of CHD1 and CHD2. |
Co-immunoprecipitation, domain truncation mapping, mutagenesis, ChIP-seq, cryptic transcription assays |
Nucleic acids research |
High |
40867051
|
| 2025 |
In mammalian cells, RTF1 facilitates histone H2B monoubiquitination (H2Bub1) via its HMD domain for Th17 cell differentiation; Rtf1 deficiency selectively disrupts Th17 differentiation while leaving Treg unaffected, and cells lacking the H2Bub1 E3 ligase subunit RNF40 (which physically interacts with RTF1) phenocopy the Rtf1 deficiency. |
T cell-specific knockout, H2Bub1 western blots, Th17 differentiation assays, co-immunoprecipitation (RTF1-RNF40) |
Journal of immunology |
Medium |
40073106
|
| 2025 |
In Drosophila, RTF1 physically interacts with the circadian clock transcription factor CLK, promotes CLK occupancy on per/tim promoters, and enhances H3K4me3 deposition (via SET1 complex, which also forms a complex with CLK and RTF1) at these loci to activate per transcription and sustain circadian rhythm amplitude. Human RTF1 physically interacts with BMAL1/CLOCK and affects circadian rhythms in U2OS cells. |
Co-immunoprecipitation, ChIP assays, genetic knockdown, circadian locomotion assays, period overexpression rescue |
The Journal of cell biology |
Medium |
41186576
|
| 2025 |
PAF1C (but not its dissociable subunit RTF1) is required for transcription restart after DNA damage; RTF1 stimulates H2B-K120 ubiquitylation and H3K4me3 but these histone marks are dispensable for post-repair transcription restoration, placing RTF1's histone modification activity outside the transcription restart pathway. |
siRNA knockdown, transcription restart assays (EU incorporation after UV), histone modification ChIP |
bioRxivpreprint |
Medium |
|