Background Age‐related macular degeneration (AMD) is a common degenerative eye disease that eventually leads to irreversible vision loss. CircRNAs have received increasing attention for their regulatory role in AMD. In this study, whole transcriptome sequencing identified differentially expressed circRNA (circMETTL3) in AMD. Previous studies have unlocked the potential mechanism of circMETTL3 in cancer, but its role in AMD has not been studied. Methods ARPE‐19 cells treated with H2O2 were used as the AMD cell model. The senescence, oxidative stress, and DNA damage of ARPE‐19 cells were determined by SA‐β‐gal staining, DCFH‐DA staining, and IF assay. The levels of RPE‐specific markers or mRNA levels were assessed using western blot assay. The potential mechanism of circMETTL3 was investigated by luciferase reporting assay and RIP assay. Results CircMETTL3 was revealed to decrease in AMD cell models. The addition of circMETTL3 decreased SA‐β‐gal staining and ROS production and facilitated cell viability in H2O2‐treated ARPE‐19 cells. Moreover, γH2AX and KRT18 levels were suppressed, and TJP1, BEST1, and CTNNB1 protein levels were increased by circMETTL3 addition. In addition, circMETTL3 could bind to and negatively regulate miR‐100. Overexpression of miR‐100 exacerbated senescence, oxidative stress, and DNA damage in H2O2‐treated ARPE‐19 cells, which reversed the effects of circMETTL3. Furthermore, BMPR2 was targeted by miR‐100. Overexpression of BMPR2 inhibited H2O2‐induced cell damage in ARPE‐19 cells, which reversed the effects of miR‐100. Conclusions In sum, these findings demonstrated that the circMETTL3/miR‐100/BMPR2 axis plays a vital regulatory role in AMD development.
Xiangyang Xin, Xin Zhao, Feng Ling et al.· Journal of Ophthalmology· 0 citations
Pollen wall formation requires precise coordination between tapetum differentiation, metabolism, and programmed cell death. In Arabidopsis, the microspore-derived peptide CLE19 restricts tapetal activity to maintain pollen wall homeostasis, yet how CLE19 signaling achieves developmental specificity and robustness remains unclear. Here, we identify the receptor-like kinase BARELY ANY MERISTEM 3 (BAM3) as an additional receptor for CLE19. Genetic, cytological, biochemical, and transcriptomic analyses showed that disruption of BAM3 signaling impairs tapetum differentiation, secretory homeostasis, and pollen exine patterning, resulting in selective transcriptional reprogramming during anther development. Comparative transcriptomic analyses reveal that BAM3 mediates a distinct subset of CLE19-responsive genes, including both AMS-dependent pathways governing tapetal degeneration and exine biosynthesis, and AMS-independent programs associated with flavonoid metabolism and pollen wall development. Biochemical assays, structure-guided mutagenesis, and AlphaFold3 modeling further support CLE19-dependent assembly of BAM3-SERK1/2 receptor complex, revealing a conserved molecular framework for CLE19 perception that is distinct from, yet complementary to, the previously characterized CLE19-PXL1-SERK1/2 receptor module. Together, these findings establish a dual-receptor architecture for CLE19 signaling in which BAM3 mediates a transcriptionally distinct branch of the CLE19 pathway. More broadly, this work demonstrates how combinatorial peptide-receptor usage expands the signaling capacity of a single developmental peptide to coordinate robust male reproductive development.
Wenhui Sun, S. Wang, Mengyu Li et al.· Plant Physiology· 0 citations