Alternative splicing generates variant forms of proteins for a given gene and accounts for functional redundancy or diversification. A novel RNA-binding protein, Pro-rich Coiled-coil Containing Protein 2B (PRRC2B), has been reported by multiple laboratories to mediate uORF-dependent and independent regulation of translation initiation required for cell cycle progression and proliferation. We identified two alternative spliced isoforms in human and mouse hearts and HEK293T cells, full-length (FL) and exon 16-excluded isoform ΔE16.
View Article and Find Full Text PDFTranslation of upstream open reading frames (uORFs) typically abrogates translation of main (m)ORFs. The molecular mechanism of uORF regulation in cells is not well understood. Here, we data-mined human and mouse heart ribosome profiling analyses and identified a double-stranded RNA (dsRNA) structure within the GATA4 uORF that cooperates with the start codon to augment uORF translation and inhibits mORF translation.
View Article and Find Full Text PDFUnlabelled: Translation of upstream open reading frames (uORFs) typically abrogates translation of main (m)ORFs. The molecular mechanism of uORF regulation in cells is not well understood. Here, we identified a double-stranded RNA (dsRNA) structure residing within the uORF that augments uORF translation and inhibits mORF translation.
View Article and Find Full Text PDFObjective: Converging evidence suggests that intestinal inflammation is involved in the pathogenesis of neurodegenerative diseases. Previous studies on fecal calprotectin in Parkinson's disease (PD) were limited by small sample sizes, and literature regarding intestinal inflammation in multiple system atrophy (MSA) is very scarce. We investigated the levels of fecal calprotectin, a marker of intestinal inflammation, in PD and MSA.
View Article and Find Full Text PDFMicroRNAs (miRNAs) play important roles in various biological processes. Our previous study showed that inhibition of MTOR with rapamycin treatment suppressed human endothelial cell tube formation, concomitant with the down-regulation of miR-107. Similarly, inhibition of Ztor by rapamycin also suppressed vascular development in zebrafish embryos.
View Article and Find Full Text PDFRationale: Increased protein synthesis of profibrotic genes is a common feature in cardiac fibrosis and heart failure. Despite this observation, critical factors and molecular mechanisms for translational control of profibrotic genes during cardiac fibrosis remain unclear.
Objective: To investigate the role of a bifunctional ARS (aminoacyl-tRNA synthetase), EPRS (glutamyl-prolyl-tRNA synthetase) in translational control of cardiac fibrosis.
Accumulation of senescent cells in vascular endothelium is known to contribute to vascular aging and increases the risk of developing cardiovascular diseases. The involvement of classical pathways such as p53/p21 and p16/pRB in cellular senescence are well described but there are emerging evidence supporting the increasingly important role of mammalian target of rapamycin (MTOR) as driver of cellular senescence via these pathways or other effector molecules. MicroRNAs (miRNAs) are a highly conserved group of small non-coding RNAs (18-25 nucleotides), instrumental in modulating the expression of target genes associated with various biological and cellular processes including cellular senescence.
View Article and Find Full Text PDFThe mammalian target of rapamycin (mTOR), a 289 kDa serine/threonine protein kinase of the phosphoinositide 3-kinase (PI3K)-related family is known for its role in regulating lifespan and the aging process in humans and rodents. Aging in zebrafish very much resembles aging in humans. Aged zebrafish often manifest with spinal curvature, cataracts and cognitive frailty, akin to human age-related phenotypical effects such as osteoarthritis, dwindling vision and cognitive dysfunction.
View Article and Find Full Text PDFAccumulation of senescent endothelial cells can cause endothelium dysfunction which eventually leads to age-related vascular disorders. The senescent-associated secretory phenotype (SASP) cells secrete a plethora of soluble factors that negatively influence the surrounding tissue microenvironment. The present study sought to investigate the effects of exosomes, which are nano-sized extracellular vesicles known for intercellular communications secreted by SASP cells on young endothelial cells.
View Article and Find Full Text PDFInt J Biochem Cell Biol
August 2018
Accumulation of senescent endothelial cells can contribute to endothelium dysfunction. Suppression of MTOR signaling has been shown to delay senescence but the mechanism that underpins this effect, particularly one that involves miRNAs, remains to be further defined. This study sought to identify miRNAs involved in MTORC1-mediated inhibition of replicative senescence in endothelial cells.
View Article and Find Full Text PDFmiRNAs are important regulators of cellular senescence yet the extent of their involvement remains to be investigated. We sought to identify miRNAs that are involved in cytokine-induced premature senescence (CIPS) in endothelial cells. CIPS was established in young human pulmonary microvascular endothelial cells (HMVEC-Ls) following treatment with a sublethal dose (20ng/ml) of tumor necrosis factor alpha (TNF-α) for 15days.
View Article and Find Full Text PDFAims: MicroRNAs (miRNAs) are vital in modulating lifespan and various biological processes including vascular function. The pivotal roles of mammalian target of rapamycin (mTOR) in regulating senescence and angiogenesis have been extensively described. However, the roles of its orthologue, zebrafish target of rapamycin (zTOR) in senescence and angiogenesis remain to be unravelled.
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