Thomas R. Cech
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View article: RNA-induced PRC2 inhibition depends on the sequence of bound RNA
RNA-induced PRC2 inhibition depends on the sequence of bound RNA Open
Methyltransferase PRC2 (Polycomb Repressive Complex 2) deposits histone H3K27 trimethylation to establish and maintain epigenetic gene silencing. PRC2 is precisely regulated by accessory proteins, histone post-translational modifications, …
View article: DHX36 modulates stress granule assembly independent of recruitment of mRNAs with G-quadruplex sequence motifs
DHX36 modulates stress granule assembly independent of recruitment of mRNAs with G-quadruplex sequence motifs Open
Stress granules are RNA–protein condensates that form in response to an increase in untranslating mRNPs (messenger ribonucleoproteins). Stress granules form by the condensation of mRNPs through a combination of protein–protein, protein–RNA…
View article: Impact of G-tract RNAs and the DHX36 helicase on stress granule composition and formation
Impact of G-tract RNAs and the DHX36 helicase on stress granule composition and formation Open
Stress granules are RNA-protein condensates that form in response to an increase in untranslating mRNPs. Stress granules form by the condensation of mRNPs through a combination of protein-protein, protein-RNA, and RNA-RNA interactions. Sev…
View article: RNA-induced PRC2 inhibition depends on the sequence of bound RNA
RNA-induced PRC2 inhibition depends on the sequence of bound RNA Open
SUMMARY Methyltransferase PRC2 (Polycomb Repressive Complex 2) deposits histone H3K27 trimethylation to establish and maintain epigenetic gene silencing. PRC2 is precisely regulated by accessory proteins, histone post-translational modific…
View article: Small molecule telomerase inhibitors are also potent inhibitors of telomeric C-strand synthesis
Small molecule telomerase inhibitors are also potent inhibitors of telomeric C-strand synthesis Open
Telomere replication is essential for continued proliferation of human cells, such as stem cells and cancer cells. Telomerase lengthens the telomeric G-strand, while C-strand replication is accomplished by CST–polymerase α–primase (CST–PP)…
View article: POT1 recruits and regulates CST-Polα/primase at human telomeres
POT1 recruits and regulates CST-Polα/primase at human telomeres Open
Telomere maintenance requires the extension of the G-rich telomeric repeat strand by telomerase and the fill-in synthesis of the C-rich strand by Polα/primase. At telomeres, Polα/primase is bound to Ctc1/Stn1/Ten1 (CST), a single-stranded …
View article: Transcription factors ERα and Sox2 have differing multiphasic DNA- and RNA-binding mechanisms
Transcription factors ERα and Sox2 have differing multiphasic DNA- and RNA-binding mechanisms Open
Many transcription factors (TFs) have been shown to bind RNA, leading to open questions regarding the mechanism(s) of this RNA binding and its role in regulating TF activities. Here, we use biophysical assays to interrogate the k on , k of…
View article: Small molecule telomerase inhibitors are also potent inhibitors of telomeric C-strand synthesis
Small molecule telomerase inhibitors are also potent inhibitors of telomeric C-strand synthesis Open
Telomere replication is essential for continued proliferation of human cells, such as stem cells and cancer cells. Telomerase lengthens the telomeric G-strand, while C-strand replication is accomplished by CST-polymerase α -primase (CST-PP…
View article: Transcription factors ERα and Sox2 have differing multiphasic DNA and RNA binding mechanisms
Transcription factors ERα and Sox2 have differing multiphasic DNA and RNA binding mechanisms Open
Many transcription factors (TFs) have been shown to bind RNA, leading to open questions regarding the mechanism(s) of this RNA binding and its role in regulating TF activities. Here we use biophysical assays to interrogate the k on , k off…
View article: Telomerase misbehaves after a breakup
Telomerase misbehaves after a breakup Open
Suppressing telomerase action at broken DNA preserves genome integrity
View article: Telomerase RNA structural heterogeneity in living human cells detected by DMS-MaPseq
Telomerase RNA structural heterogeneity in living human cells detected by DMS-MaPseq Open
Telomerase is a specialized reverse transcriptase that uses an intrinsic RNA subunit as the template for telomeric DNA synthesis. Biogenesis of human telomerase requires its RNA subunit (hTR) to fold into a multi-domain architecture that i…
View article: Structural basis for inactivation of PRC2 by G-quadruplex RNA
Structural basis for inactivation of PRC2 by G-quadruplex RNA Open
Polycomb repressive complex 2 (PRC2) silences genes through trimethylation of histone H3K27. PRC2 associates with numerous precursor messenger RNAs (pre-mRNAs) and long noncoding RNAs (lncRNAs) with a binding preference for G-quadruplex RN…
View article: Evaluation of the RNA-dependence of PRC2 binding to chromatin in human pluripotent stem cells
Evaluation of the RNA-dependence of PRC2 binding to chromatin in human pluripotent stem cells Open
Polycomb Repressive Complex 2 (PRC2), an important histone modifier and epigenetic repressor, has been known to interact with RNA for almost two decades. In our previous publication (Long, Hwang et al. 2020), we presented data supporting t…
View article: PRC2 direct transfer from G-quadruplex RNA to dsDNA has implications for RNA-binding chromatin modifiers
PRC2 direct transfer from G-quadruplex RNA to dsDNA has implications for RNA-binding chromatin modifiers Open
The chromatin-modifying enzyme, Polycomb Repressive Complex 2 (PRC2), deposits the H3K27me3 epigenetic mark to negatively regulate expression at numerous target genes, and this activity has been implicated in embryonic development, cell di…
View article: Supplementary Figures 1-8 from Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers
Supplementary Figures 1-8 from Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers Open
Fig. S1. Projecting the individual TERTp mutations transcriptional signatures on top of the Onco-GPS map of cellular states (Kim et al. 2017). Fig.S2. Association between the different mRNA signatures analyzed in this study. Fig S3. Expres…
View article: Data from Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers
Data from Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers Open
In a substantial fraction of cancers TERT promoter (TERTp) mutations drive expression of the catalytic subunit of telomerase, contributing to their proliferative immortality. We conducted a pan-cancer analysis of cell lines and find a TERT…
View article: Supplementary Methods and Table S1 from Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers
Supplementary Methods and Table S1 from Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers Open
Table S1. TERTp mutations included in this study
View article: Supplementary Methods and Table S1 from Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers
Supplementary Methods and Table S1 from Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers Open
Table S1. TERTp mutations included in this study
View article: Supplementary Figures 1-8 from Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers
Supplementary Figures 1-8 from Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers Open
Fig. S1. Projecting the individual TERTp mutations transcriptional signatures on top of the Onco-GPS map of cellular states (Kim et al. 2017). Fig.S2. Association between the different mRNA signatures analyzed in this study. Fig S3. Expres…
View article: Data from Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers
Data from Mesenchymal and MAPK Expression Signatures Associate with Telomerase Promoter Mutations in Multiple Cancers Open
In a substantial fraction of cancers TERT promoter (TERTp) mutations drive expression of the catalytic subunit of telomerase, contributing to their proliferative immortality. We conducted a pan-cancer analysis of cell lines and find a TERT…
View article: Structural basis for inactivation of PRC2 by G-quadruplex RNA
Structural basis for inactivation of PRC2 by G-quadruplex RNA Open
The histone methyltransferase PRC2 (Polycomb Repressive Complex 2) silences genes via successively attaching three methyl groups to lysine 27 of histone H3. PRC2 associates with numerous pre-mRNA and lncRNA transcripts with a binding prefe…
View article: DNMT1 inhibition by pUG-fold quadruplex RNA
DNMT1 inhibition by pUG-fold quadruplex RNA Open
Aberrant DNA methylation is one of the earliest hallmarks of cancer. DNMT1 is responsible for methylating newly replicated DNA, but the precise regulation of DNMT1 to ensure faithful DNA methylation remains poorly understood. A link betwee…
View article: TIRF Microscopy Data Files: "RNA- and DNA-Binding Proteins Exhibit a General Mechanism for Direct Transfer of Polynucleotides: Implications for Target Site Search"
TIRF Microscopy Data Files: "RNA- and DNA-Binding Proteins Exhibit a General Mechanism for Direct Transfer of Polynucleotides: Implications for Target Site Search" Open
TIRF-microscopy images and analysis data from single-molecule experiments assessing the direct transfer phenomenon in the TREX1 exonuclease.
View article: DNMT1 inhibition by pUG-fold quadruplex RNA
DNMT1 inhibition by pUG-fold quadruplex RNA Open
Aberrant DNA methylation is one of the earliest hallmarks of cancer. DNMT1 is responsible for methylating newly replicated DNA, but the precise regulation of DNMT1 to ensure faithful DNA methylation remains poorly understood. A link betwee…
View article: Polycomb-mediated genome architecture enables long-range spreading of H3K27 methylation
Polycomb-mediated genome architecture enables long-range spreading of H3K27 methylation Open
Significance The relationship between long-range Polycomb-associated chromatin contacts and the linear propagation of histone H3 lysine 27 trimethylation (H3K27me3) by Polycomb repressive complex 2 (PRC2) is not well-characterized. Here, w…
View article: TIRF Microscopy Data Files. "Multiple RNA- and DNA-binding proteins exhibit direct transfer of polynucleotides: Implications for target site search"
TIRF Microscopy Data Files. "Multiple RNA- and DNA-binding proteins exhibit direct transfer of polynucleotides: Implications for target site search" Open
TIRF-microscopy images and analysis data from single-molecule experiments assessing the direct transfer phenomenon in the TREX1 exonuclease.