bims-polyam 2024-02-11 papers

Issue of 2024‒02‒11
two papers selected by
Sebastian J. Hofer, University of Graz

Int J Mol Sci. 2024 Feb 01. pii: 1766. [Epub ahead of print]25(3):

The Deficiency of Hypusinated eIF5A Decreases the Putrescine/Spermidine Ratio and Inhibits +1 Programmed Ribosomal Frameshifting during the Translation of Ty1 Retrotransposon in Saccharomyces cerevisiae.

Yu Xiao, Ruanlin Wang, Xiaxia Han, Wei Wang, Aihua Liang.

Programmed ribosomal frameshifting (PRF) exists in all branches of life that regulate gene expression at the translational level. The eukaryotic translation initiation factor 5A (eIF5A) is a highly conserved protein essential in all eukaryotes. It is identified initially as an initiation factor and functions broadly in translation elongation and termination. The hypusination of eIF5A is specifically required for +1 PRF at the shifty site derived from the ornithine decarboxylase antizyme 1 (OAZ1) in Saccharomyces cerevisiae. However, whether the regulation of +1 PRF by yeast eIF5A is universal remains unknown. Here, we found that Sc-eIF5A depletion decreased the putrescine/spermidine ratio. The re-introduction of Sc-eIF5A in yeast eIF5A mutants recovered the putrescine/spermidine ratio. In addition, the Sc-eIF5A depletion decreases +1 PRF during the decoding of Ty1 retrotransposon mRNA, but has no effect on -1 PRF during the decoding of L-A virus mRNA. The re-introduction of Sc-eIF5A in yeast eIF5A mutants restored the +1 PRF rate of Ty1. The inhibition of the hypusine modification of yeast eIF5A by GC7 treatment or by mutating the hypusination site Lys to Arg caused decreases of +1 PRF rates in the Ty1 retrotransposon. Furthermore, mutational studies of the Ty1 frameshifting element support a model where the efficient removal of ribosomal subunits at the first Ty1 frame 0 stop codon is required for the frameshifting of trailing ribosomes. This dependency is likely due to the unique position of the frame 0 stop codon distance from the slippery sequence of Ty1. The results showed that eIF5A is a trans-regulator of +1 PRF for Ty1 retrotransposon and could function universally in yeast.

Keywords: Saccharomyces cerevisiae; Ty1 retrotransposon; eIF5A; programmed ribosomal frameshifting

DOI: https://doi.org/10.3390/ijms25031766

Clin Immunol. 2024 Feb 07. pii: S1521-6616(24)00039-1. [Epub ahead of print] 109928

Age-specific Metabolomic profiles in children with food allergy.

E Crestani, M Benamar, W Phipatanakul, R Rachid, T A Chatila.

BACKGROUND: Food allergy (FA) in young children is often associated with eczema, frequently directed to egg/cow milk allergens and has a higher chance of resolution, while FA that persists in older children has less chance of resolution and is less clearly associated with atopy.METHODS: Children with FA (n = 62) and healthy controls (n = 28) were categorized into "younger" (≤5 years) and "older" (>5 years). Mass spectrometry-based untargeted metabolomic profiling as wells as cytokine profiling were performed on plasma samples in FA children in each age group.
RESULTS: Younger FA children manifested unique alterations in bile acids, polyamine metabolites and chemokines associated with Th2 responses, while older FA children displayed pronounced changes in long chain fatty acids, acylcarnitines and proinflammatory cytokines.
CONCLUSIONS: FA children of different ages manifest unique metabolic changes which may reflect at least in part pathogenic mechanisms and environmental influences operative at different time points in the disease course.

Keywords: Age; Bile acids; Food allergy; Metabolomics; PUFAs; Polyamines

DOI: https://doi.org/10.1016/j.clim.2024.109928