Chandramohan, R. | Search bioRxiv

bioRxiv2024

The ELF3-BBX24/BBX25-PIF4 module controls thermosensory growth in Arabidopsis

Temperature serves as a crucial environmental cue governing the growth and adaptation of plants in their natural habitat. PHYTOCHROME INTERACTING FACTOR 4 (PIF4) is a central regulator that promotes thermomorphogenesis in Arabidopsis. Understanding its precise regulation is critical for optimal thermomorphogenic growth. Here, we identified two BBX proteins, BBX24 and BBX25, as novel components of the PIF4-mediated thermosensory pathway and act to promote warm temperature-mediated growth. The bbx24 and bbx25 single and double mutants showed moderate to strong temperature-insensitive hypocotyl and cotyledon growth. Warm temperature induces BBX24 and BBX25 mRNA expression and protein accumulation. Genetic and biochemical analysis revealed that BBX24/BBX25 promotes PIF4-mediated thermosensory growth by counteracting a key component of the evening complex, ELF3. While ELF3 inhibits BBX24/BBX25 gene expression at low ambient temperatures in the evening, warm temperature-mediated inhibition of ELF3 activity results in enhanced BBX24/BBX25 activity. Moreover, BBX24/25 inhibit ELF3 function through direct physical interaction and likely relieves repression on PIF4, enhancing its activity and thermomorphogenesis. Together, this study unravels ELF3-BBX24/BBX25-PIF4 as a key regulatory module that controls growth and development under varying temperature cues.

plant biology↗

bioRxiv2018

Genetic evidence that the latency III stage of Epstein-Barr Virus infection is a therapeutic target for Multiple Sclerosis

Genome wide association studies have identified >200 susceptibility loci accounting for much of the heritability of Multiple Sclerosis (MS). Epstein Barr virus (EBV), a memory B cell tropic virus, has been identified as necessary but not sufficient for development of MS, with evidence for disease causation. The molecular and immunological basis for this has not been established. LCL proliferation is driven by signalling through the EBV produced cell surface protein LMP1, a homologue of the MS risk gene CD40. We show that the CD40 ligand, CD40L, potentially through competitive signalling with LMP1, reduces LCL proliferation (p<0.001). The MS risk variants of the LMP1 signalling inhibitor, TRAF3, had altered expression in B cells and LCLs. Both CD40 and TRAF3 risk SNPs are in binding sites for the EBV transcription factor EBNA2. We have investigated transcriptomes of B cells and EBV infected B cells at Latency III (LCLs) and identified 47 MS risk genes with altered expression, associated with the risk genotype. Overall these MS risk SNPs were overrepresented in target loci of the EBV transcription factor EBNA2 (p<10-16), in genes dysregulated between B and LCLs (p<10-5), and as targets for EBV miRNAs (p<10-4). The risk gene ZC3HAV1 is the putative target for multiple EBV miRNAs. It amplifies the interferon response, and was shown to have reduced expression in LCLs for the risk allele. These data indicate targeting EBV EBNA2, miRNAs, and MS risk genes on the LMP1/LMP2 pathways, and the pathways themselves, may be of therapeutic benefit in MS.

genomics↗