Journal: Cell reports

Article Title: Mutant KRAS-driven selective mRNA translation reveals mechanisms and therapeutic vulnerabilities in cancer

doi: 10.1016/j.celrep.2026.117520

Figure Lengend Snippet: (A and B) TE fold change analysis of common transcripts affected by sotorasib and CR-1-31B shows that mutant KRAS and EIF4A oppositely regulate the translation of these mRNAs. Most of the sotorasib TE down targets are TE upregulated following EIF4A inhibition with CR-1-31B. (C) TE fold change analysis of common translation factors between sotorasib and CR-1-31B reveals the upregulation of all the translation factors following CR-1-31B treatment, except for four proteins that are downregulated by CR-1-31B. (D and E) Relative luciferase activity driven by G-quadruplex (GQ) and GC-rich motifs in response to sotorasib, RMC-7977, or MRTX1133 treatment demonstrates that sotorasib induces GQ and GC-rich mRNA translation ( * p < 0.05 and *** p < 0.001). (F and G) Luciferase reporter assays using the full-length or mutated 5′UTR of EEF1A1 show altered luciferase activity upon CR-1-31B and Torin1 treatment in MiaPaca-2 cells (* p < 0.05 and *** p < 0.001). (H) Combination treatment of CR-1-31B and Torin1 with mutant KRAS inhibitors in a panel of cancer cell lines harboring either G12C or G12D KRAS mutations leads to an additive enhancement of cell death, based on the zero interaction potency (ZIP) model. (I) Summary of our findings shows that the mutant KRAS-dependent mechanism of translational control uncouples the regulation of translation machinery from the regulation of the rest of the mRNA translation. Mutant KRAS-dependent mechanism is distinct from the mTOR and EIF4A-dependent mechanism that depends on longer and structured 5′UTR features and controls the translation of a distinct subset of mRNAs.

Article Snippet: Torin1 , MedChemExpress , Cat# HY-13003.

Techniques: Mutagenesis, Inhibition, Luciferase, Activity Assay, Control

Journal: Life Science Alliance

Article Title: A microRNA generated via lysosomal processing of ribosomal RNA suppresses proinflammatory responses

doi: 10.26508/lsa.202503536

Figure Lengend Snippet: (A, B, C, D) HFF cells were kept in basal conditions (t = 0) or starved (t = 4) in the absence (CTRL) or presence of either (A) 0.3 μM SAR405, (B) 50 nM bafilomycin A (BAF), (C) 20 μM chloroquine (CQ), or (D) cells were not starved but instead treated with 200 nM Torin-1 (depicting results only at t = 4). The expression of miR-21-5p and miR-4488 was quantified by RT–qPCR. Relative quantity (RQ) was calculated by normalizing the relative expression of the miRNA in starved cells to its expression in control cells (t = 0). For statistical analysis procedures, see legend to .

Article Snippet: Chloroquine (C6628; Sigma-Aldrich), bafilomycin A1 (BML-CM110-0100; Enzo), SAR405 (533063; Sigma-Aldrich), and Torin-1 (inh-tor1; InvivoGen) were added to the fresh medium at the onset of the treatment.

Techniques: Expressing, Quantitative RT-PCR, Control

Journal: Life Science Alliance

Article Title: A microRNA generated via lysosomal processing of ribosomal RNA suppresses proinflammatory responses

doi: 10.26508/lsa.202503536

Figure Lengend Snippet: (A) Schematic representation of the pre-miR-4488 sequence, highlighting in blue circles the first 18 nucleotides of the mature miRNA and in red circles the sequence of the primer detecting the pre-miR-4488. (B) Control HFFs or HFFs treated with 200 nM Torin-1 for 4 h were harvested and processed for subcellular fractionation as described in the Materials and Methods section. Cytosolic and lysosome-containing fractions were subjected to RNA extraction, and the relative amounts of pre-miR-4488 were determined by RT–qPCR, using the pre-miR-4488–derived primer.

Article Snippet: Chloroquine (C6628; Sigma-Aldrich), bafilomycin A1 (BML-CM110-0100; Enzo), SAR405 (533063; Sigma-Aldrich), and Torin-1 (inh-tor1; InvivoGen) were added to the fresh medium at the onset of the treatment.

Techniques: Sequencing, Control, Fractionation, RNA Extraction, Quantitative RT-PCR, Derivative Assay