Nascent RNA interaction keeps PRC2 activity poised and in check.
Genes & Development 28(18):1983 (2014)
Polycomb-repressive complex 2 (PRC2) facilitates the maintenance and inheritance of chromatin domains repressive to transcription through catalysis of methylation of histone H3 at Lys27 (H3K27me2/3). However, through its EZH2 subunit, PRC2 also binds to nascent transcripts from active genes that...
Jarid2 Is Implicated in the Initial Xist-Induced Targeting of PRC2 to the Inactive X Chromosome.
Molecular Cell 53(2):301 (2014)
During X chromosome inactivation (XCI), the Polycomb Repressive Complex 2 (PRC2) is thought to participate in the early maintenance of the inactive state. Although Xist RNA is essential for the recruitment of PRC2 to the X chromosome, the precise mechanism remains unclear. Here, we demonstrate t...
Interactions between JARID2 and noncoding RNAs regulate PRC2 recruitment to chromatin.
Molecular Cell 53(2):290 (2014)
JARID2 is an accessory component of Polycomb repressive complex-2 (PRC2) required for the differentiation of embryonic stem cells (ESCs). A role for JARID2 in the recruitment of PRC2 to target genes silenced during differentiation has been put forward, but the molecular details remain unclear. W...
IgA nephropathy caused by unusual polymerization of IgA1 with aberrant N-glycosylation in a patient with monoclonal immunoglobulin deposition disease.
PLoS ONE 9(3):e91079 (2014)
Immunoglobulin A nephropathy (IgAN) is a form of chronic glomerulonephritis characterized by the deposition of IgA immune complexes in the glomerular region. The cause of IgAN is unknown, but multiple mechanisms have been suggested. We previously reported a rare case of mesangioproliferative glo...
PRC2 binds active promoters and contacts nascent RNAs in embryonic stem cells.
Nature Structural & Molecular Biology 20(11):1258 (2013)
EZH2 is the catalytic subunit of PRC2, a central epigenetic repressor essential for development processes in vivo and for the differentiation of embryonic stem cells (ESCs) in vitro. The biochemical function of PRC2 in depositing repressive H3K27me3 marks is well understood, but how it is regula...
Phosphorylation of the PRC2 component Ezh2 is cell cycle-regulated and up-regulates its binding to ncRNA.
Genes & Development 24(23):2615 (2010)
Ezh2 functions as a histone H3 Lys 27 (H3K27) methyltransferase when comprising the Polycomb-Repressive Complex 2 (PRC2). Trimethylation of H3K27 (H3K27me3) correlates with transcriptionally repressed chromatin. The means by which PRC2 targets specific chromatin regions is currently unclear, but...
The tumor suppressor Cdc73 functionally associates with CPSF and CstF 3' mRNA processing factors.
PNAS 106(3):755 (2009)
The CDC73 tumor suppressor gene is mutationally inactivated in hereditary and sporadic parathyroid tumors. Its product, the Cdc73 protein, is a component of the RNA polymerase II and chromatin-associated human Paf1 complex (Paf1C). Here, we show that Cdc73 physically associates with the cleavage...
Human capping enzyme promotes formation of transcriptional R loops in vitro.
PNAS 104(45):17620 (2007)
Cap formation is the first step of pre-mRNA processing in eukaryotic cells. Immediately after transcription initiation, capping enzyme (CE) is recruited to RNA polymerase II (Pol II) by the phosphorylated carboxyl-terminal domain of the Pol II largest subunit (CTD), allowing cotranscriptional ca...
The multifunctional protein p54nrb/PSF recruits the exonuclease XRN2 to facilitate pre-mRNA 3' processing and transcription termination.
Genes & Development 21(14):1779 (2007)
Termination of RNA polymerase II transcription frequently requires a poly(A) signal and cleavage/polyadenylation factors. Recent work has shown that degradation of the downstream cleaved RNA by the exonuclease XRN2 promotes termination, but how XRN2 functions with 3'-processing factors to elicit...
Polyadenylation factor CPSF-73 is the pre-mRNA 3'-end-processing endonuclease.
Nature 444(7121):953 (2006)
Most eukaryotic messenger RNA precursors (pre-mRNAs) undergo extensive maturational processing, including cleavage and polyadenylation at the 3'-end. Despite the characterization of many proteins that are required for the cleavage reaction, the identity of the endonuclease is not known. Recent a...
Terminating the transcript: breaking up is hard to do.
Genes & Development 20(9):1050 (2006)
The mammalian RNA polymerase II C-terminal domain interacts with RNA to suppress transcription-coupled 3' end formation.
Molecular Cell 20(1):91 (2005)
RNA polymerase II plays a critical role not only in transcription of mRNA precursors but also in their subsequent processing. This later function is mediated primarily by the C-terminal domain (CTD) of the enzyme's largest subunit, a unique, repetitive structure conserved throughout eukaryotes a...
BRCA1/BARD1 inhibition of mRNA 3' processing involves targeted degradation of RNA polymerase II.
Genes & Development 19(10):1227 (2005)
Mammalian cells exhibit a complex response to DNA damage. The tumor suppressor BRCA1 and associated protein BARD1 are thought to play an important role in this response, and our previous work demonstrated that this includes transient inhibition of the pre-mRNA 3' processing machinery. Here we pr...
Requirements of the RNA polymerase II C-terminal domain for reconstituting pre-mRNA 3' cleavage.
Molecular and Cellular Biology 22(6):1684 (2002)
RNA polymerase II (RNAP II) has previously been shown to be required for the pre-mRNA polyadenylation cleavage reaction in vitro. This activity was found to reside solely in the C-terminal domain (CTD) of the enzyme's largest subunit. Using a deletion analysis of glutathione S-transferase-CTD fu...