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科研成果: “PTBP1 induces ADAR1 p110 isoform expression through IRES-like dependent translation control and influences cell proliferation in gliomas.”彭小忠组
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       彭小忠课题组课题组在《Cell Mol Life Sci》 杂志发表研究论文“PTBP1 induces ADAR1 p110 isoform expression through IRES-like dependent translation control and influences cell proliferation in gliomas. (2015)”。

       RNA编辑酶ADAR1在生理和病理过程中扮演着重要的角色。本文研究ADAR1对神经胶质瘤发生发展的影响。中国医学科学院基础医学研究所,“医学分子生物学国家重点实验室”的彭小忠课题组课题组发现在胶质瘤细胞中ADAR1 p110可以通过IRES样的元件被PTBP1激活从而影响胶质瘤细胞的增殖。

     【摘要】:Internal ribosomal entry site (IRES)-mediated translation initiation is constitutively activated during stress conditions such as tumorigenesis and hypoxia. The RNA editing enzyme ADAR1 plays an important role in physiology and pathology. Initially, we found that  the ADAR1 p150 or p110 transcript levels were decreased in glioma cells compared with normal astrocyte cells. In contrast, protein levels of ADAR1 p110 were significantly upregulated in glioma tissues and cells. This expression pattern indicated translationally controlled regulation. We identified an 885-nt sequence that was located between AUG1 and AUG2 within the ADAR1 mRNA that exhibited IRES-like activity. Furthermore, we confirmed that the translational mode of ADAR1 p110 was mediated by PTBP1 in glioma cells. The protein levels of PTBP1 and ADAR1 were cooperatively expressed in glioma tissues and cells. Knocking down ADAR1 p110 significantly decreased cell proliferation in three types of glioma cells (T98G, U87MG and A172). The removal of a minimal IRES-like sequence in a p150-overexpression construct could effectively abolish p110 induction and resulted in the slight suppression of cell proliferation compared with ADAR1-p150 overexpression in siPTBP1-treated T98G cells. In summary, our study revealed a mechanism whereby ADAR1 p110 can be activated by PTBP1 through an IRES-like element in glioma cells, and ADAR1 is essential for the maintenance of gliomagenesis.

 

相关结果已发表于《Cell Mol Life Sci》 杂志(2015,72(22):4383-97.),其作者为彭小忠课题组课题组博士研究生杨彬,重点室彭小忠研究员是本文的通讯作者。该研究工作得到了以下基金的支持:973、国家自然基金