caa a22 4500 606175768 CHVBK 20210128100744.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s00018-015-1938-7 doi (NATIONALLICENCE)springer-10.1007/s00018-015-1938-7 PTBP1 induces ADAR1 p110 isoform expression through IRES-like dependent translation control and influences cell proliferation in gliomas [Elektronische Daten] [Bin Yang, Peishan Hu, Xihua Lin, Wei Han, Liyuan Zhu, Xiaochao Tan, Fei Ye, Guanzhou Wang, Fan Wu, Bin Yin, Zhaoshi Bao, Tao Jiang, Jiangang Yuan, Boqin Qiang, Xiaozhong Peng] 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. Springer Basel, 2015 ADAR1 nationallicence PTBP1 nationallicence IRES-like nationallicence Cell proliferation nationallicence Gliomas nationallicence Yang Bin The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut Hu Peishan The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut Lin Xihua The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut Han Wei The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut Zhu Liyuan The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut Tan Xiaochao The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut Ye Fei The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut Wang Guanzhou The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut Wu Fan The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut Yin Bin The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut Bao Zhaoshi Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, 100050, Beijing, People's Republic of China aut Jiang Tao Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, 100050, Beijing, People's Republic of China aut Yuan Jiangang The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut Qiang Boqin The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut Peng Xiaozhong The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut Cellular and Molecular Life Sciences Springer Basel 72/22(2015-11-01), 4383-4397 1420-682X 72:22<4383 2015 72 18 https://doi.org/10.1007/s00018-015-1938-7 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-015-1938-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yang Bin The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Hu Peishan The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Lin Xihua The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Han Wei The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Zhu Liyuan The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Tan Xiaochao The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Ye Fei The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Wang Guanzhou The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Wu Fan The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Yin Bin The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Bao Zhaoshi Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, 100050, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Jiang Tao Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, 100050, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Yuan Jiangang The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Qiang Boqin The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut NATIONALLICENCE 700 1- Peng Xiaozhong The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, 100005, Beijing, People's Republic of China aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/22(2015-11-01), 4383-4397 1420-682X 72:22<4383 2015 72 18