Maf1 Cooperates with Progesterone Receptor to Repress RNA Polymerase III Transcription of Select tRNAs.

Progesterone receptors (PR) can regulate transcription by RNA Polymerase III (Pol III), which transcribes small non-coding RNAs, including all transfer RNAs (tRNAs). We have previously demonstrated that PR is associated with the Pol III complex at tRNA genes and that progestins downregulate tRNA transcripts in breast tumor models. To further elucidate the mechanism of PR-mediated regulation of Pol III, we studied the interplay between PR, the Pol III repressor Maf1, and TFIIIB, a core transcription component.

A randomized, double-blind, placebo-controlled, multiple dose, parallel study to investigate the effects of a cathepsin S inhibitor in celiac disease.

Celiac disease is a chronic, immune-mediated enteropathy with symptoms triggered by exposure to dietary gluten in genetically predisposed individuals. The only available management option is lifelong adherence to a gluten-free diet. This randomized, double-blind, placebo-controlled, parallel-group, single-center study tested the effects of the cathepsin S inhibitor RO5459072 on the immune response to a 13-day gluten challenge in 19 participants with celiac disease (ClinicalTrials.

Identifying barriers and opportunities to facilitate the uptake of whole genome sequencing in paediatric haematology and oncology practice.

Background: The clinical utility of whole genome sequencing (WGS) in paediatric cancer has been demonstrated in recent years. WGS has been routinely available in the National Health Service (NHS) England for all children with cancer in England since 2021, but its uptake has been variable geographically. To explore the underlying barriers to routine use of WGS in this population across England and more widely in the United Kingdom (UK) and the Republic of Ireland (ROI), a one-day workshop was held in Cambridge, United Kingdom in October 2022.

Redundant pathways for removal of defective RNA polymerase II complexes at a promoter-proximal pause checkpoint.

The biological purpose of Integrator and RNA polymerase II (RNAPII) promoter-proximal pausing remains uncertain. Here, we show that loss of INTS6 in human cells results in increased interaction of RNAPII with proteins that can mediate its dissociation from the DNA template, including the CRL3 E3 ligase, which ubiquitylates CTD serine-phosphorylated RPB1 for degradation. ARMC5-dependent RNAPII ubiquitylation is activated by defects in factors acting at the promoter-proximal pause, including Integrator, DSIF, and capping enzyme.