Biology subjects

Pan, J.-Q.

Publications and source records attributed to Pan, J.-Q..

3 recordsLinked to original sources

bioRxiv2026

Paraspeckles translate microbial insult-induced inflammation into neurovascular remodeling by enhancing CYR61-FGF2 signaling via RBM14 sequestration

BackgroundSystemic inflammation triggered by microbial insults can disrupt endothelial homeostasis, impair blood-brain and blood-retinal barriers, leading to neurovascular remodeling in the central nervous system (CNS). Subnuclear condensates, paraspeckles, play a substantial role in stress-induced gene regulation, yet their contribution to the inflammatory relay from microbial insults to neurovascular remodeling remains unelucidated. ResultsOur comparative transcriptomic analysis followed by experimental validation identified a cross-species NEAT1_2/CYR61/FGF2 signature in the CNS positively associated with neurovascular remodeling across human disease cohorts and multiple mouse models. Notably, systemic inflammation triggered by microbial insults, including sepsis or gut dysbiosis, enhanced NEAT1_2 expression in the brain and retina with neurovascular remodeling. Microbial insults induced hyper-assembly of paraspeckles and the expression of CYR61 and FGF2 in vascular endothelial cells. Paraspeckle assembly and its required NEAT1_2 Domain C, rather than NEAT1_2 expression levels, play a pivotal role in endothelial homeostasis control and neurovascular remodeling by sequestering the RNA-binding protein RBM14 from the CYR61 promoter, thereby relieving its repression of CYR61 transcription. Moreover, secreted CYR61 enhanced FGF2-mediated endothelial remodeling signals in a paracrine manner. Disrupting paraspeckle assembly by targeting Domain C intercepts neurovascular remodeling, restoring endothelial homeostasis in vivo. ConclusionsOur results demonstrate an essential and conserved role for paraspeckles in the inflammatory relay from microbial insults to neurovascular remodeling by sequestering RBM14 to enhance CYR61-FGF2 signaling. Furthermore, our study underscores paraspeckle assembly as a promising therapeutic target for neurovascular remodeling and related diseases.

molecular biology↗

bioRxiv2024

Multi-tissue transition of A-to-I RNA editing pattern and its regulatory relevance in transcription, splicing, and translation during development

Previous studies have shown that A-to-I RNA editing can occur in various organs and tissues under normal physiological conditions. However, the dynamics of RNA editing and its functional relevance in multiple tissues and organs during the embryo-to-adult transition in mammals remain to be elucidated. Here, we performed a comprehensive analysis of RNA-Seq and Ribo-Seq data from six mouse tissues at embryonic and adult stages to elucidate the A-to-I RNA editing transition during development and to validate it in additional mouse brain datasets spanning multiple developmental stages. Our results revealed a general transition of up-regulated A-to-I RNA editing activity across numerous tissue types during embryonic-adult development, indicated by significantly increased average RNA editing levels. Consistently, differential RNA editing (DRE) analysis showed more up-regulated than down-regulated RNA editing sites in all six tissue types. Furthermore, such RNA editing transitions during development could contribute to differential gene expression (DEG) at both transcriptional and translational levels, as well as differential alternative splicing (DAS) across multiple tissues. Differentially edited genes with DEG or DAS could be involved not only in tissue-specific biological functions but also in common routine biological processes during development. Notably, Adarb1 was found to be a more important player than Adar in the CNS (the brain and retina), with its expression levels increasing gradually and correlating with the A-to-I RNA editing activity. Our study demonstrates the potential role of A-to-I editing during development across multiple tissues, providing new insights into its regulatory relevance in both transcriptional and translational landscapes.

genomics↗

bioRxiv2020

Novel missense mutation E585K in retinitis pigmentosa leads to compromised RPGR splicing diversity

Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene, are the major cause of X-linked retinitis pigmentosa (RP). Herein we used whole-exome sequencing to screen possible novel RPGR mutations in RP patients, and identified a novel missense mutation E585K in a patient with early onset but slow disease progression, and a frameshift deletion E998Gfs*78 in a patient with RP sine pigmento and high myopia. Intriguingly, bioinformatic analysis indicated that E585K probably affected RPGR RNA splicing instead of the protein sequence directly. Mini-gene assays in 293T cells revealed that splicing events of the E585K mutant were found to be also exist in wildtype, but with a shifted pattern. In the E585K mini-gene usage of an upstream alternative 5' splice site (5' ss) of exon 14 was enhanced, and other splicing events were suppressed, including the canonical 5' ss of exon 14, skipping of exon 14/15 and retention of intron 14. As a result, RPGR splicing products of the E585K mini-gene were predominated by transcripts containing a 4-bp deletion, with a small fraction of in-frame transcripts containing a retended intron 14, which might explain the slow disease progression in the patient carrying the mutation. RNA-Seq analysis further confirmed existence of these splicing events in endogenous RPGR RNA in human retina, pointing to compromised splicing diversity in the E585K mutant. Our findings thus added to the understanding of genotype-phenotype correlation in RP, and suggested that compromised RPGR splicing diversity might play a role in molecular mechanism of the disease.

genetics↗