Search bioRxiv⌕ Search

Biology subjects

Abbas, S. H.

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

2 recordsLinked to original sources

Ambivalent roles of nonsense-mediated mRNA decay in heat stress tolerance

RNA homeostasis is essential for gene regulation and cellular survival; however, how RNA degradation pathways contribute to stress adaptation remains incompletely understood. Here, we investigated the role of the nonsense-mediated mRNA decay (NMD) in regulating heat stress (HS) memory in a long-term acquired thermotolerance assay. NMD-deficient Arabidopsis thaliana mutants upf1-5 and upf3-1 exhibited a biphasic phenotype: they displayed transiently elevated heat tolerance during early recovery but became more sensitive to heat during late recovery. Genetic analysis of upf3;hsfa2 and upf3;hsfa3 double mutants demonstrated that the early heat tolerance occurs independently of both HsfA2 and HsfA3 HS-memory transcription factors. Under non-treated conditions, the upf3-1 transcriptome exhibited baseline priming of heat-shock responsive transcripts, likely accounting for the initial heat tolerance. Further transcriptome profiling revealed that upf3-1 mutants exhibited reduced levels of the functional HsfA2 isoform (HsfA2-I) and attenuated expression of the HsfA2-dependent thermomemory regulon following the triggering stress. NMD deficiency also upregulated immune-response genes while repressing developmental and cell-wall-associated pathways. Together, impaired HsfA2-dependent thermomemory and a compromised growth defense balance underlies the late heat sensitivity of NMD deficient plants. Overall, NMD acts as a dual-action post-transcriptional regulator that coordinates the transition from stress response to growth resumption.

plant biology↗

Machine perfusion and single-cell spatial transcriptome mapping identifies novel immune escape mechanisms in colorectal cancer liver metastasis

Liver metastasis is the terminal stage of colorectal cancer. Immune checkpoint blockade (ICB) has heralded remarkable clinical success across a range of cancer types, but with limited efficacy in replacement-type colorectal liver metastasis (CRLM), the most common and lethal histological subtype. Using a novel human normothermic perfusion model, we demonstrate for the first time, that T-cells preferentially extravasate within the peri-tumoural liver rather than the CRLM. We use single-cell spatial transcriptomics and multiplexed immunofluorescence to validate CRLM T-cell exclusion and show that CRLM endothelia are anergic, lacking key receptors required for T-cell extravasation. CD4 T-cells that extravasate within the peri-tumoural liver are TCR-reactive, yet exhausted, whilst CD4 T-cells within the CRLM demonstrate a stress response, impaired cytokine expression and lack of TCR reactivity. We identify the spatial cellular and molecular interactions underlying these observations, providing novel targets for future attempts to sensitise to immunotherapeutics and a justification for failed ICB efficacy in CRLM.

cancer biology↗