T. R. Cech

Small molecule telomerase inhibitors are also potent inhibitors of telomeric C-strand synthesis

The paper shows that telomerase inhibitors TMPyP4 and PDS also inhibit telomeric C-strand synthesis by stabilizing DNA structures and blocking CST-PP binding.

Transcription factors ERα and Sox2 have differing multiphasic DNA and RNA binding mechanisms

This study investigates the DNA and RNA binding kinetics of ERα and Sox2, revealing distinct multiphasic binding mechanisms with ER showing novel triphasic association behavior.

Telomerase RNA structural heterogeneity in living human cells detected by DMS-MaPseq

This study identifies a misfolded CR4/5 conformation in hTR that is not required for hTERT binding and is detrimental to telomerase activity.

Structural basis for inactivation of PRC2 by G-quadruplex RNA

The paper presents a cryo-EM structure of PRC2 bound to G-quadruplex RNA, revealing how RNA inhibits PRC2 by promoting dimerization and blocking DNA interaction.

RNA- and DNA-binding proteins generally exhibit direct transfer of polynucleotides: Implications for target site search

The paper demonstrates that RNA- and DNA-binding proteins can directly transfer polynucleotides, enabling one-dimensional target site search and suggesting regulated complex lifetimes in vivo.

PRC2 direct transfer from G-quadruplex RNA to dsDNA: Implications for RNA-binding chromatin modifiers

This study reveals a direct transfer mechanism by which PRC2 exchanges RNA and DNA/nucleosome in its binding site, reconciling conflicting in vitro and in vivo findings on RNA's role in regulating PRC2 activity.

DNMT1 inhibition by pUG-fold quadruplex RNA

This study shows that DNMT1 interacts with pUG-fold RNA, which inhibits its activity by blocking DNA binding.

CST does not evict elongating telomerase but prevents initiation by ssDNA binding

The paper investigates CST's role in telomerase inhibition and shows it does not terminate ongoing telomerase extension but prevents initiation through ssDNA binding.

Nuclear compartmentalization of TERT mRNA and TUG1 lncRNA transcripts is driven by intron retention: implications for RNA-directed therapies

The paper shows that intron retention drives nuclear compartmentalization of TERT mRNA and TUG1 lncRNA, impacting cell growth and suggesting new RNA-based therapy targets.

The cryo-EM structure of human CST reveals a two-megadalton decameric assembly bound to telomeric DNA

The paper reports the cryo-EM structure of human CST bound to telomeric DNA, revealing a decameric supercomplex and providing insights into CST function and disease associations.

Single-cell imaging reveals unexpected heterogeneity of TERT expression across cancer cell lines

The paper uses single-molecule RNA FISH to analyze TERT expression in cancer cell lines, revealing cell-to-cell variation, complex gene expression patterns, and unexpected nuclear localization of TERT mRNA.

Regulation of histone methylation by automethylation of PRC2

This study identifies EZH2 automethylation as a regulatory mechanism that modulates PRC2 histone methyltransferase activity.

Dynamics of human telomerase recruitment depend on template-telomere base-pairing

This study uses live-cell imaging to show that telomerase recruitment depends on DNA base-pairing and processivity in human cells.