The HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE15-HISTONE DEACETYLASE9 complex associates with HYPONASTIC LEAVES 1 to modulate microRNA expression in response to abscisic acid signaling.

The regulation of microRNA (miRNA) biogenesis is crucial for maintaining plant homeostasis under biotic and abiotic stress. The crosstalk between the RNA polymerase II (Pol-II) complex and the miRNA processing machinery has emerged as a central hub modulating transcription and cotranscriptional processing of primary miRNA transcripts (pri-miRNAs). However, it remains unclear how miRNA-specific transcriptional regulators recognize MIRNA loci. Here, we show that the Arabidopsis (Arabidopsis thaliana) HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE15 (HOS15)-HISTONE DEACETYLASE9 (HDA9) complex is a conditional suppressor of miRNA biogenesis, particularly in response to abscisic acid (ABA). When treated with ABA, hos15/hda9 mutants show enhanced transcription of pri-miRNAs that is accompanied by increased processing, leading to overaccumulation of a set of mature miRNAs. Moreover, upon recognition of the nascent pri-miRNAs, the ABA-induced recruitment of the HOS15-HDA9 complex to MIRNA loci is guided by HYPONASTIC LEAVES 1 (HYL1). The HYL1-dependent recruitment of the HOS15-HDA9 complex to MIRNA loci suppresses expression of MIRNAs and processing of pri-miRNA. Most importantly, our findings indicate that nascent pri-miRNAs serve as scaffolds for recruiting transcriptional regulators, specifically to MIRNA loci. This indicates that RNA molecules can act as regulators of their own expression by causing a negative feedback loop that turns off their transcription, providing a self-buffering system.

ABA INSENSITIVE 2 promotes flowering by inhibiting OST1/ABI5-dependent FLOWERING LOCUS C transcription in Arabidopsis.

The plant hormone abscisic acid (ABA) is an important regulator of plant growth and development and plays a crucial role in both biotic and abiotic stress responses. ABA modulates flowering time, but the precise molecular mechanism remains poorly understood. Here we report that ABA INSENSITIVE 2 (ABI2) is the only phosphatase from the ABA-signaling core that positively regulates the transition to flowering in Arabidopsis. Loss-of-function abi2-2 mutant shows significantly delayed flowering both under long day and short day conditions. Expression of floral repressor genes such as FLOWERING LOCUS C (FLC) and CYCLING DOF FACTOR 1 (CDF1) was significantly up-regulated in abi2-2 plants while expression of the flowering promoting genes FLOWERING LOCUS T (FT) and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 (SOC1) was down-regulated. Through genetic interactions we further found that ost1-3 and abi5-1 mutations are epistatic to abi2-2, as both of them individually rescued the late flowering phenotype of abi2-2. Interestingly, phosphorylation and protein stability of ABA INSENSITIVE 5 (ABI5) were enhanced in abi2-2 plants suggesting that ABI2 dephosphorylates ABI5, thereby reducing protein stability and the capacity to induce FLC expression. Our findings uncovered the unexpected role of ABI2 in promoting flowering by inhibiting ABI5-mediated FLC expression in Arabidopsis.

GIGANTEA-ENHANCED EM LEVEL complex initiates drought escape response via dual function of ABA synthesis and flowering promotion.

Plants use the regulation of their circadian clock to adapt to daily environmental challenges, particularly water scarcity. During drought, plants accelerate flowering through a process called drought escape (DE) response, which is promoted by the circadian clock component GIGANTEA (GI). GI up-regulates the flowering inducer gene FLOWERING LOCUS T (FT). Phytohormone Abscisic acid (ABA) is also required for drought escape, and both GIGANTEA and Abscisic acid are interdependent in the transition. Recent research has revealed a new mechanism by which GIGANTEA and the protein ENHANCED EM LEVEL form a heterodimer complex that turns on ABA biosynthesis during drought stress by regulating the transcription of 9-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (NCED3). This highlights the close connection between the circadian clock and ABA regulation and reveals a new adaptive strategy for plants to cope with drought and initiates the DE response.

Negative regulation of floral transition in Arabidopsis by HOS15-PWR-HDA9 complex.

Arabidopsis HOS15/PWR/HDA9 repressor complex, which is similar to the TBL1/NcoR1/HDAC complex in animals, plays a well-known role in epigenetic regulation. PWR and HDA9 have been reported to interact with each other and modulate the flowering time by repressing AGL19 expression, whereas HOS15 and HDA9, together with the photoperiodic evening complex, regulate flowering time through repression of GI transcription. However, the role of the HOS15/PWR/HDA9 core repressor complex as a functional unit in the regulation of flowering time is yet to be explored. In this study, we reported that the loss-of-function hos15-2/pwr/hda9 triple mutant accumulates higher transcript levels of AGL19 and exhibits an early flowering phenotype similar to those of hos15, pwr, and hda9 single mutants. Interestingly, the accumulation of HOS15 in the nucleus was drastically reduced in pwr and hda9 mutants. As a result, HOS15 could not perform its role in histone deacetylation or interaction with H3 in the nucleus. Furthermore, HOS15 is also associated with the same region of the AGL19 promoter known for PWR-HDA9 binding. The acetylation level of the AGL19 promoter was increased in the hos15-2 mutant, similar to the pwr and hda9 mutants. Therefore, our findings reveal that the HOS15/PWR/HDA9 repressor complex deacetylates the promoter region of AGL19, thereby negatively regulating AGL19 transcription, which leads to early flowering in Arabidopsis.

Possible Pharmacodynamic Interaction of Azelnidipine with Citicoline Against Ischemic Brain Injury: Behavioral, Biochemical and Histological Alterations.

BACKGROUND: Currently, no drug has been approved for the management of postischemic neuronal damage. Existing studies show that calcium channel blockers have neuroprotective properties, while citicoline is involved in maintaining neuronal integrity. PURPOSE: This study was envisaged to investigate the effect of azelnidipine (novel calcium channel blocker) alone and in combination with citicoline (phosphatidyl-choline analogue) against ischemic brain damage in Wistar rats. METHODS: Previously standardized bilateral common carotid artery occlusion model was used to induce cerebral ischemic injury in Wistar rats. Pretreatment with azelnidipine (1.5 mg/Kg and 3 mg/Kg; p.o.) or citicoline (250 mg/Kg; i.p.) was done every 24 h starting 7 days before the bilateral common carotid artery occlusion surgery. Pharmacological assessments (behavioral, biochemical, mitochondrial, molecular, and histological) were done after 48 h of the reperfusion period. RESULTS: Azelnidipine and citicoline were found to protect the brain from progressive neuronal damage as seen by improved sensorimotor behavior (locomotion, rota rod, and beam balance performance) and reduced oxidative stress (decreased malondialdehyde (MDA), nitrite, increased glutathione (GSH), superoxide dismutase (SOD)). Impairment of mitochondrial enzyme system and increase in the infarct area were found to be arrested by individual treatments with azelnidipine and citicoline. These effects were further potentiated synergistically as the combination of citicoline and azelnidipine was found to decrease glutamate levels, caspase-3 activity and histological alterations as compared to their individual effects. CONCLUSION: Azelnidipine and citicoline synergistically decrease excitotoxic and oxidative damage against ischemic brain injury in Wistar rats and, therefore, propose a clinically relevant combination for the prevention of postischemic neuronal damage.