Biology subjects

Stricker, S. H.

Publications and source records attributed to Stricker, S. H..

2 recordsLinked to original sources

bioRxiv2026

A pre-rRNA positive feedback loop drives malignant ribosome biogenesis

Altered nucleoli are a well-established hallmark of cancer1, but how oncogenic signalling remodels the nucleolus remains poorly understood. Here we used an inducible mouse model of pancreatic ductal adenocarcinoma (PDAC)2 to generate spatially resolved proteomic and phosphoproteomic maps of the nucleolus upon RAS oncogene activation. We identify a phosphorylation programme initiated by translocation of the Casein Kinase 2 (CK2) holoenzyme to the nucleolus. This programme amplifies rRNA synthesis and malignant ribosome biogenesis by phosphorylating factors that control RNA polymerase I transcription and early ribosomal RNA (rRNA) processing. Preventing the nucleolar activity of CK2 inhibits oncogene-induced rRNA production, while constitutive nucleolar trapping of CK2 is sufficient to activate rRNA synthesis in the absence of RAS oncogene. Mechanistically, CK2 accumulation in the nucleolus is mediated by direct binding to the 3 External Transcribed Sequence (3ETS) of nascent precursor rRNA, creating an RNA-dependent self-amplifying feedback loop. Nucleolar CK2 accumulation is conserved across diverse human cancers, and its disruption synergises with inhibition of oncogenic RAS signalling to suppress anchorage-independent growth and tumourigenesis. Our study reveals 3ETS as a CK2 signalling scaffold that amplifies oncogenic ribosome biogenesis, and defines a druggable nucleolar vulnerability that can be exploited by targeting this process.

cancer biology↗

bioRxiv2024

SLAM-seq reveals independent contributions of RNA processing and stability to gene expression in African trypanosomes

Gene expression is a multi-step process that converts DNA-encoded information into proteins, involving RNA transcription, maturation, degradation, and translation. While transcriptional control is a major regulator of protein levels, the role of post-transcriptional processes such as RNA processing and degradation is less well understood due to the challenge of measuring their contributions individually. To address this challenge, we investigated the control of gene expression in Trypanosoma brucei, a unicellular parasite assumed to lack transcriptional control. Instead, mRNA levels in T. brucei are controlled by post-transcriptional processes, which enabled us to disentangle the contribution of both processes to total mRNA levels. In this study, we developed an efficient metabolic RNA labeling approach and combined ultra-short metabolic labeling with transient transcriptome sequencing (TT-seq) to confirm the long-standing assumption that RNA polymerase II transcription is unregulated in T. brucei. In addition, we established thiol (SH)-linked alkylation for metabolic sequencing of RNA (SLAM-seq) to globally quantify RNA processing rates and half-lives. Our data, combined with scRNA-seq data, indicate that RNA processing and stability independently affect total mRNA levels and contribute to the variability seen between individual cells in African trypanosomes.

molecular biology↗