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1.
Proc Natl Acad Sci U S A ; 117(13): 7245-7254, 2020 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-32170011

RESUMO

Lens transparency is established by abundant accumulation of crystallin proteins and loss of organelles in the fiber cells. It requires an efficient translation of lens messenger RNAs (mRNAs) to overcome the progressively reduced transcriptional activity that results from denucleation. Inappropriate regulation of this process impairs lens differentiation and causes cataract formation. However, the regulatory mechanism promoting protein synthesis from lens-expressed mRNAs remains unclear. Here we show that in zebrafish, the RNA-binding protein Rbm24 is critically required for the accumulation of crystallin proteins and terminal differentiation of lens fiber cells. In the developing lens, Rbm24 binds to a wide spectrum of lens-specific mRNAs through the RNA recognition motif and interacts with cytoplasmic polyadenylation element-binding protein (Cpeb1b) and cytoplasmic poly(A)-binding protein (Pabpc1l) through the C-terminal region. Loss of Rbm24 reduces the stability of a subset of lens mRNAs encoding heat shock proteins and shortens the poly(A) tail length of crystallin mRNAs encoding lens structural components, thereby preventing their translation into functional proteins. This severely impairs lens transparency and results in blindness. Consistent with its highly conserved expression in differentiating lens fiber cells, the findings suggest that vertebrate Rbm24 represents a key regulator of cytoplasmic polyadenylation and plays an essential role in the posttranscriptional control of lens development.


Assuntos
Cristalinas/metabolismo , Cristalino/metabolismo , Proteínas de Ligação a RNA/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Catarata/metabolismo , Cristalinas/genética , Citoplasma/metabolismo , Modelos Animais , Poliadenilação , Processamento Pós-Transcricional do RNA , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/genética , Fatores de Transcrição/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/genética
2.
Asian J Androl ; 19(5): 561-566, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27624986

RESUMO

Polychlorinated biphenyls (PCBs) are common environmental contaminants that represent a considerable risk to reproductive toxicity in exposed human populations. Although some experimental studies have suggested an association between the levels of PCBs and semen quality, the direct effects of PCBs on human sperm parameters remain largely unexplored. To this aim, a short-term in vitro incubation experiment that better imitated the putative exposure of sperm to Aroclor 1254 (a commercial PCB mixture) in male reproduction tissue was conducted. Human sperm were incubated with various concentrations (0, 1, 5, or 25 mg l-1) of Aroclor 1254 for different amounts of time (3 and 6 h) in vitro. Sperm motility parameters were analyzed with computer-assisted sperm analysis (CASA). The proportion of sperm with high mitochondrial membrane potential (ΔΨm) and the levels of intracellular reactive oxygen species (ROS) were detected to explore the probable cause of sperm impairment. Human sperm exposed to continuous Aroclor 1254 exhibited: (i) reduced sperm motility and kinematic parameters, (ii) a proportion of sperm with high ΔΨm that decreased in a dose-dependent manner (P < 0.05), and (iii) increased levels of ROS compared with controls (P < 0.05). In conclusion, Aroclor 1254 can decrease sperm motility, which may culminate in increased ROS and general mitochondrial dysfunction, thus affecting the fertilization potential of sperm. Our findings suggest a broader understanding of the effect of Aroclor 1254 on human sperm.


Assuntos
/toxicidade , Poluentes Ambientais/toxicidade , Motilidade dos Espermatozoides/efeitos dos fármacos , Adulto , Fenômenos Biomecânicos , Relação Dose-Resposta a Droga , Humanos , Técnicas In Vitro , Masculino , Potencial da Membrana Mitocondrial , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
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