RNA Biology最新文献

Exonic circular RNAs (ecircRNAs) in animal cells are generated by backsplicing, and the biogenesis of ecircRNAs is regulated by an array of RNA binding proteins (RBPs). HNRNPD is a heterogeneous nuclear ribonucleoprotein family member with both cytoplasmic and nuclear roles, and whether HNRNPD regulates the biogenesis of circRNAs remains unknown. In this study, we examine the role of HNRNPD in the biogenesis of ecircRNAs. The levels of ecircRNAs are primarily increased upon depletion of HNRNPD. HNRNPD preferentially binds to motifs enriched with A and U nucleotides, and the flanking introns of ecircRNAs tend to have more numbers and higher intensity of HNRNPD binding sites. The levels of mRNAs are generally not significantly altered in HNRNPD knockout cells. For a small set of genes, the circRNA:mRNA ratio is substantially affected, and the mRNA levels of some of these genes demonstrate a significant decrease in HNRNPD knockout cells. CDK1 is identified as a key gene modulated by HNRNPD in the context of circRNA biogenesis. HNRNPD suppresses the biogenesis of circCDK1 and favours the generation of CDK1 mRNA, and the CDK1 protein is a critical regulator of the cell cycle and apoptosis. HNRNPD can participate in cellular physiology, including the cell cycle and apoptosis, and plays roles in clear cell renal cell carcinoma (ccRCC) by modulating circRNA biogenesis and the mRNA levels of key genes, such as CDK1.

In Escherichia coli, transport of magnesium ions across the cellular membrane relies on MgtA and CorA transporters. While the expression of mgtA is controlled by the two-component system PhoQ/PhoP and 5' upstream region elements, corA expression is considered to be constitutive and not to depend on cellular factors. Importantly, the 5' upstream region of corA is predicted to fold into structures highly similar to the magnesium-sensing mgtA 5' upstream region. Here using biochemical and genetic assays, we show that the intracellular concentration of magnesium ions affects corA expression. Similarly to mgtA, we find that the effect of magnesium ions on corA expression is mediated by the 5' upstream region. We demonstrate that the RNA structure is important for regulation and that the Rho transcription factor is involved in the modulation of transcription termination. Consistent with previous studies, we find that translation of corL, a short ORF located within the 5' upstream region, is important for corA regulation. Our data indicate that the efficiency of corL translation is inversely proportional to corA expression, similar to what has been described for mgtA and corA in Salmonella enterica. Using a novel assay to control the import of magnesium ions, we show that while the expression of mgtA is regulated by both extra- and intracellular magnesium ions, corA is regulated by variations in intracellular magnesium ions. Our results support a model in which the expression of corA is regulated by the 5' upstream region that senses variations of intracellular magnesium ions.

A 60-year-old otherwise healthy male presented with a 1 year history of bilateral progressive visual loss. His best-corrected visual acuity was counting fingers at 2 m with his right eye and counting fingers at 0.5 m with his left eye. Visual field testing revealed bilateral near-total loss of visual fields. Slit-lamp examination was unremarkable, apart from bilateral grade two nuclear sclerotic cataracts. Both optic discs were pale-looking with some retinal pigment epithelial alterations at the left papillomacular region. Enhanced depth imaging optical coherence tomography depicted punctate hyperreflective dots at the inner choroidal level corresponding to the retinal pigment epithelial changes in the left eye. Fundus autofluorescence imaging revealed patchy hyper-autofluorescent and hypo-autofluorescent areas, and there was mild staining in the early and late phases of the fluorescein angiogram at the papillomacular region in the left eye. A diagnosis of bilateral optic neuropathy was made. A full systemic work-up was carried out, and serological tests pointed out the presence of syphilis with normal cranial magnetic resonance imaging. He was treated accordingly. Our case clearly demonstrates the importance of a high clinical suspicion for syphilis in cases of optic neuropathy.