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Identification of the internal ribosome entry sites (IRES) of prion protein gene
Affiliation:1. State Key Laboratory of Infectious Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China;2. Inner Mongolia Medical University, Huhehot, China;1. Intercollege Graduate Degree Program in Physiology, United States of America;2. Department of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA, United States of America;1. Department of Radiology, UT Southwestern Medical Center, Dallas, TX 75390, USA;2. Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA;1. Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland;2. Department of Molecular Medicine, Sapienza University, 00161 Rome, Italy
Abstract:Many studies demonstrated that there are several type bands of prion protein in cells. However, the formation of different prion protein bands is elusive. After several low molecular weight bands of prion protein appeared in SMB-S15 cells infected with scrapie agent Chandler, we think that IRES-dependent translation mechanism induced by prion is involved in the formation of prion protein bands. Then we designed a series of pPrP-GFP fusing plasmids and bicistronic plasmids to identify the IRES sites of prion protein gene and found 3 IRES sites inside of PrP mRNA. We also demonstrated that cap-independent translation of PrP was associated with the ER stress through Tunicamycin treatment. We still found that only IRE1 and PERK pathway regulated the IRES-dependent translation of PrP in this study. Our results indicated, we found that PrP gene had an IRES-dependent translation initiation mechanism and we successfully identified the IRESs inside of the prion protein gene.
Keywords:Prion protein gene  IRES  Translation mechanism
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