title: Translational regulation of RPA2 via internal ribosomal entry site and by eIF3a.
abstract: RPA2 is a subunit of a trimeric replication protein A (RPA) complex important for DNA repair and replication. Although it is known that RPA activity is regulated by post-translational modification, whether RPA expression is regulated and the mechanism therein is currently unknown. eIF3a, the largest subunit of eIF3, is an important player in translational control and has been suggested to regulate translation of a subset of messenger RNAs important for tumorigenesis, metastasis, cell cycle progression, drug response and DNA repair. In the present study, we show that RPA2 expression is regulated at translational level via internal ribosome entry site (IRES)-mediated initiation in response to DNA damage. We also found that eIF3a suppresses RPA2 synthesis and inhibits its cellular IRES activity by directly binding to the IRES element of RPA2 located at -50 to -150 bases upstream of the translation start site. Taken together, we conclude that RPA2 expression is translationally regulated via IRES and by eIF3a and that this regulation is partly accountable for cellular response to DNA damage and survival.
authors: Department of Pharmacology/Toxicology, IU Simon Cancer Center, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors: Ji-Ye
authors: JY
authors: Yin
authors: Zi-Zheng
authors: ZZ
authors: Dong
authors: Ran-Yi
authors: RY
authors: Liu
authors: Juan
authors: J
authors: Chen
authors: Zhao-Qian
authors: ZQ
authors: Liu
authors: Jian-Ting
authors: JT
authors: Zhang
mesh_terms: D016475:3T3 Cells; D020121:5' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair; D004268:DNA-Binding Proteins; D039621:Eukaryotic Initiation Factor-3 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011485:Protein Binding; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics; D051716:Replication Protein A / Q000096:biosynthesis* / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA
chemical_list: D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; C105988:EIF3A protein, human; D039621:Eukaryotic Initiation Factor-3; D012333:RNA, Messenger; D051716:Replication Protein A; C516794:RPA2 protein, human
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