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1.
Int J Mol Sci ; 25(10)2024 May 10.
Article de Anglais | MEDLINE | ID: mdl-38791231

RÉSUMÉ

Ribosomal RNAs (rRNAs) are extensively modified during the transcription and subsequent maturation. Three types of modifications, 2'-O-methylation of ribose moiety, pseudouridylation, and base modifications, are introduced either by a snoRNA-driven mechanism or by stand-alone enzymes. Modified nucleotides are clustered at the functionally important sites, including peptidyl transferase center (PTC). Therefore, it has been hypothesised that the modified nucleotides play an important role in ensuring the functionality of the ribosome. In this study, we demonstrate that seven 25S rRNA modifications, including four evolutionarily conserved modifications, in the proximity of PTC can be simultaneously depleted without loss of cell viability. Yeast mutants lacking three snoRNA genes (snR34, snR52, and snR65) and/or expressing enzymatically inactive variants of spb1(D52A/E679K) and nop2(C424A/C478A) were constructed. The results show that rRNA modifications in PTC contribute collectively to efficient translation in eukaryotic cells. The deficiency of seven modified nucleotides in 25S rRNA resulted in reduced cell growth, cold sensitivity, decreased translation levels, and hyperaccurate translation, as indicated by the reduced missense and nonsense suppression. The modification m5C2870 is crucial in the absence of the other six modified nucleotides. Thus, the pattern of rRNA-modified nucleotides around the PTC is essential for optimal ribosomal translational activity and translational fidelity.


Sujet(s)
Peptidyl transferases , Biosynthèse des protéines , ARN ribosomique , Saccharomyces cerevisiae , ARN ribosomique/génétique , ARN ribosomique/métabolisme , Saccharomyces cerevisiae/génétique , Saccharomyces cerevisiae/métabolisme , Peptidyl transferases/métabolisme , Peptidyl transferases/génétique , Protéines de Saccharomyces cerevisiae/génétique , Protéines de Saccharomyces cerevisiae/métabolisme , Saccharomycetales/génétique , Saccharomycetales/métabolisme , Ribosomes/métabolisme , Petit ARN nucléolaire/génétique , Petit ARN nucléolaire/métabolisme , Maturation post-transcriptionnelle des ARN , ARN fongique/génétique , ARN fongique/métabolisme , Mutation
2.
Clin Chem Lab Med ; 62(3): 442-452, 2024 Feb 26.
Article de Anglais | MEDLINE | ID: mdl-37776061

RÉSUMÉ

OBJECTIVES: The aim of the study was to determine the diagnostic performance of novel automated red cell parameters for estimating bone marrow iron stores. METHODS: The study was a retrospective single-centre study based on data from an automated haematology analyser and results of bone marrow iron staining. Red cell parameters were measured on a Sysmex XN-series haematology analyser. Bone marrow iron stores were assessed semiquantitatively by cytochemical reaction according to Perls. RESULTS: The analysis included 429 bone marrow aspirate smears from 393 patients. Median age of patients was 67 years, 52 % of them were female. The most common indication for bone marrow examination was a plasma cell dyscrasia (n=104; 24 %). Median values of percentage of hypochromic and hyperchromic red blood cells (%HYPO-He, %HYPER-He), reticulocyte haemoglobin equivalent (RET-He) and microcytic red blood cells (MicroR) were statistically significantly different between cases with iron deplete and iron replete bone marrow. In a logistic regression model, ferritin was the best predictor of bone marrow iron stores (AUC=0.891), outperforming RET-He and %HYPER-He (AUC=0.736 and AUC=0.722, respectively). In a combined model, ferritin/MicroR index achieved the highest diagnostic accuracy (AUC=0.915), outperforming sTfR/log ferritin index (AUC=0.855). CONCLUSIONS: While single automated red cell parameters did not show improved diagnostic accuracy when compared to traditional iron biomarkers, a novel index ferritin/MicroR has the potential to outperform ferritin and sTfR/log ferritin index for predicting bone marrow iron stores. Further research is needed for interpretation and implementation of novel parameters and indices, especially in the context of unexplained anaemia and myelodysplastic syndromes.


Sujet(s)
Anémie par carence en fer , Humains , Femelle , Sujet âgé , Mâle , Anémie par carence en fer/diagnostic , Moelle osseuse , Études rétrospectives , Fer/métabolisme , Ferritines , Hémoglobines/analyse
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