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1.
Nucleic Acids Res ; 46(12): 6304-6317, 2018 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-29618122

RESUMO

Among the proteins predicted to be a part of the DExD box RNA helicase family, the functions of DDX49 are unknown. Here, we characterize the enzymatic activities and functions of DDX49 by comparing its properties with the well-studied RNA helicase, DDX39B. We find that DDX49 exhibits a robust ATPase and RNA helicase activity, significantly higher than that of DDX39B. DDX49 is required for the efficient export of poly (A)+ RNA from nucleus in a splicing-independent manner. Furthermore, DDX49 is a resident protein of nucleolus and regulates the steady state levels of pre-ribosomal RNA by regulating its transcription and stability. These dual functions of regulating mRNA export and pre-ribosomal RNA levels enable DDX49 to modulate global translation. Phenotypically, DDX49 promotes proliferation and colony forming potential of cells. Strikingly, DDX49 is significantly elevated in diverse cancer types suggesting that the increased abundance of DDX49 has a role in oncogenic transformation of cells. Taken together, this study shows the physiological role of DDX49 in regulating distinct steps of mRNA and pre-ribosomal RNA metabolism and hence translation and potential pathological role of its dysregulation, especially in cancers.


Assuntos
RNA Helicases DEAD-box/metabolismo , Biossíntese de Proteínas , RNA Helicases/metabolismo , Precursores de RNA/metabolismo , RNA Mensageiro/metabolismo , RNA Ribossômico/metabolismo , Trifosfato de Adenosina/metabolismo , Carcinogênese , Linhagem Celular , Nucléolo Celular/enzimologia , Nucléolo Celular/genética , Proliferação de Células , RNA Helicases DEAD-box/genética , Humanos , Precursores de RNA/biossíntese , Estabilidade de RNA , Transporte de RNA
2.
J Biomed Mater Res B Appl Biomater ; 108(4): 1546-1558, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31609522

RESUMO

The present study explores the possibility of Zn2+ substituted calcium zirconium phosphate [CaZr4 (PO4 )6 ] as a potential replacement for the existing materials in load bearing orthopedic applications. Pure CaZr4 (PO4 )6 ) and wide range of Zn2+ substitutions in CaZr4 (PO4 )6 have been synthesized through citrate assisted sol-gel technique. The characterization results confirmed the extraordinary structural stability displayed by CaZr4 (PO4 )6 until 1,550°C. Further, the flexibility of CaZr4 (PO4 )6 lattice to accommodate 40 mol% of Zn2+ has been determined. The microstructures of CaZr4 (PO4 )6 and Zn2+ substituted CaZr4 (PO4 )6 demonstrated irregular sized grains and cracks alongside the negligence to obtain definite grain boundaries. This has been reflected in the moderate mechanical properties of the investigated specimen; nevertheless, Zn2+ substituted CaZr4 (PO4 )6 displayed enhanced mechanical stability. Further, in vitro tests signified the remarkable biocompatibility and alkaline phosphatase activity of Zn2+ substituted CaZr4 (PO4 )6 .


Assuntos
Materiais Biocompatíveis , Fosfatos de Cálcio , Teste de Materiais , Zircônio , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Linhagem Celular Tumoral , Humanos , Zircônio/química , Zircônio/farmacologia
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