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Evidence for low-level translation in human erythrocytes.

ABSTRACT: It is generally believed that human mature erythrocytes do not possess functional ribosomes and therefore cannot synthesize proteins. However, the absence of translation is not consistent with the long lifespan of mature erythrocytes. They stay viable and functional for about 115 d in the circulatory system. Here, using a highly pure preparation of human mature erythrocytes, we demonstrate the presence of translation by polysome profiling, [³⁵S]methionine labeling, and RiboPuromycylation. [³⁵S]methionine labeling revealed that the translation in mature erythrocytes is about 10% of that observed in reticulocytes. We could observe polysomes by transmission electron microscopy in these cells. RNA-seq and quantitative real-time PCR performed on polysome fractions of these cells revealed that HBA (α-globin) and HBB (β-globin) transcripts are translated. Using a luciferase-based reporter assay and mutational studies, we show that the sequence of the 5' untranslated region is crucial for the translation of these transcripts. Furthermore, mature erythrocytes showed reduced expression of globin proteins (α- and β-) when treated with translation inhibitors. Overall, we provide multiple lines of evidence for translation of globin mRNAs in human mature erythrocytes.

SUBMITTER: Kumar SD

PROVIDER: S-EPMC9635303 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Evidence for low-level translation in human erythrocytes.

Kumar Sangeetha Devi SD Kar Debaleena D Akhtar Md Noor MN Willard Belinda B Roy Debadrita D Hussain Tanweer T Rajyaguru Purusharth I PI Eswarappa Sandeep M SM

Molecular biology of the cell 20220817 12

It is generally believed that human mature erythrocytes do not possess functional ribosomes and therefore cannot synthesize proteins. However, the absence of translation is not consistent with the long lifespan of mature erythrocytes. They stay viable and functional for about 115 d in the circulatory system. Here, using a highly pure preparation of human mature erythrocytes, we demonstrate the presence of translation by polysome profiling, [<sup>35</sup>S]methionine labeling, and RiboPuromycylat ...[more]

PMID: 35976696

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Project description:BackgroundMethylmercury (MeHg) is a known neuro-toxicant. Emerging evidence indicates it may have adverse effects on the neuro-logic and other body systems at common low levels of exposure. Impacts of MeHg exposure could vary by individual susceptibility or be confounded by beneficial nutrients in fish containing MeHg. Despite its global relevance, synthesis of the available literature on low-level MeHg exposure has been limited.ObjectivesWe undertook a synthesis of the current knowledge on the human health effects of low-level MeHg exposure to provide a basis for future research efforts, risk assessment, and exposure remediation policies worldwide.Data sources and extractionWe reviewed the published literature for original human epidemiologic research articles that reported a direct biomarker of mercury exposure. To focus on high-quality studies and those specifically on low mercury exposure, we excluded case series, as well as studies of populations with unusually high fish consumption (e.g., the Seychelles), marine mammal consumption (e.g., the Faroe Islands, circumpolar, and other indigenous populations), or consumption of highly contaminated fish (e.g., gold-mining regions in the Amazon).Data synthesisRecent evidence raises the possibility of effects of low-level MeHg exposure on fetal growth among susceptible subgroups and on infant growth in the first 2 years of life. Low-level effects of MeHg on neuro-logic outcomes may differ by age, sex, and timing of exposure. No clear pattern has been observed for cardio-vascular disease (CVD) risk across populations or for specific CVD end points. For the few studies evaluating immunologic effects associated with MeHg, results have been inconsistent.ConclusionsStudies targeted at identifying potential mechanisms of low-level MeHg effects and characterizing individual susceptibility, sexual dimorphism, and non-linearity in dose response would help guide future prevention, policy, and regulatory efforts surrounding MeHg exposure.

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Evidence for low-level translation in human erythrocytes.

Publications

Evidence for low-level translation in human erythrocytes.

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