Biology subjects

Bjerke, G.

Publications and source records attributed to Bjerke, G..

3 recordsLinked to original sources

bioRxiv2026

Coordinated inhibition of SOX9 and cell cycle progression by microRNA-200 restricts sebaceous gland fate specification

The microRNA-200 family (miR-200s) is widely recognized for their potent role in inhibiting epithelial-to-mesenchymal transition and cell cycle progression in cancer. However, their functional specificity in normal epithelial development remains poorly understood. Here we show that miR-200s are highly enriched in hair matrix progenitors but conspicuously absent from the upper hair follicle (HF), the anatomical location where sebaceous gland (SG) and HF stem cells are specified. We demonstrate that elevated miR-200 expression in this region abolishes SG fate specification while permitting hair morphogenesis. Genome-wide identification of miR-200 targets reveals that miR-200s regulate multiple negative regulators of WNT signaling, in addition to cell cycle regulators. Single-cell and spatial transcriptomic analyses uncover a mutually exclusive expression patterns between WNT activity and SOX9 in the upper HF, which is disrupted by miR-200 induction, resulting in compromised SOX9 function. Mechanistically, genome-wide identification of SOX9 targets uncovers a broad network of lipid and fatty acid metabolism genes critical for the transition of upper HF progenitors to the SG fate. The coordinated inhibition of the SOX9-dependent lipogenic program and the potent restriction of cell cycle progression, both mediated by miR-200s, collectively blocks SG specification. Taken together, this work reveals an unexpected specificity of miR-200 in restricting epithelial plasticity and elucidates a spatially defined SOX9 regulatory network essential for SG development.

developmental biology↗

bioRxiv2025

Compartmentalization of mRNA and Translation by Desmosomes

Subcellular compartmentalization enables cells to concentrate and locally regulate functions. Here we find that translational machinery is compartmentalized to the cell cortex in epidermal cells. Furthermore, we observed broad enrichment of transcripts at the cortex, establishing a novel axis of mRNA organization in these cells. Mechanistically, we identified the desmosomal protein, desmoplakin, to be essential for cortical recruitment of both ribosomes and mRNAs, through distinct mechanisms. While mRNA localization is usually proposed to promote local translation, we found that most cortical transcripts were translationally repressed. These findings reveal spatial and transcript-dependent features of the cortical translatome. One mediator of this regulation is the RNA-induced Silencing Complex (RISC) which is also cortically enriched in a desmoplakin-dependent manner. Under homeostatic conditions, cortical RISC associates with transcripts for cell adhesion and the cytoskeleton. Upon wounding RISC is delocalized from the cortex and its associated transcripts become translationally upregulated. Together our data demonstrate a desmosome-dependent cortical compartmentalization of translation that dynamically responds to barrier perturbations, including wounding.

cell biology↗

bioRxiv2019

Integrated analysis of directly captured microRNA targets reveals the impact of microRNAs on mammalian transcriptome

MicroRNA (miRNA)-mediated regulation is widespread, relatively mild but functionally important. Despite extensive efforts to identify miRNA targets, it remains unclear how miRNAs bind to mRNA targets globally and how changes in miRNA levels affects the transcriptome. Here we apply an optimized method for simultaneously capturing miRNA and targeted RNA sites to wildtype, miRNA knockout and induced epithelial cells. We find that abundantly expressed miRNAs can bind to thousands of different transcripts and many different miRNAs can regulate the same gene. Although mRNA sites that are bound by miRNAs and also contain matches to seed sequences confer the strongest regulation, [~]50% of miRNAs bind to RNA regions without seed matches. In general, these bindings have little impact on mRNA levels and reflect a scanning activity of miRNAs. In addition, different miRNAs have different preferences to seed matches and 3end base-pairing. For a single miRNA, the effectiveness of mRNA regulation is highly correlated with the number of captured miRNA:RNA fragments. Notably, elevated miRNA expression effectively represses existing targets with little impact on newly recognized targets. Global analysis of directly captured mRNA targets reveals pathways that are involved in cancer, cell adhesion and signaling pathways are highly regulated by many different miRNAs in epithelial cells. Comparison between experimentally captured and TargetScan predicted targets indicates that our approach is more effective to identify bona fide targets by reducing false positive and negative predictions. This study reveals the global binding landscape and impact of miRNAs on mammalian transcriptome.

molecular biology↗