The UV-inducible RNA-binding protein A18 (A18 hnRNP) plays a protective role in the genotoxic stress response.
We have previously shown that specific RNA-binding proteins (RBP) are activated by genotoxic stress. The role and function of these stress-activated RBP are, however, poorly understood. The data presented here indicate that the RBP A18 heterogeneous ribonucleoprotein (hnRNP) is induced and translocated from the nuclei to the cytoplasm after exposure to UV radiation. Using a new in vitro system we identified potential cellular targets for A18 hnRNP. Forty-six mRNA transcripts were identified, most of which are stress- or UV-responsive genes. Two important stress-responsive transcripts, the replication protein A (RPA2) and thioredoxin, were studied in more detail. Northwestern analyses indicate that A18 hnRNP binds specifically to the 3'-untranslated region of RPA2 transcript independently of its poly(A) tail, whereas the poly(A) tail of thioredoxin mRNA reinforces binding. Overexpression of A18 hnRNP increases the mRNAs stability and consequently enhances translation in a dose-dependent manner. Moreover, cell lines expressing reduced levels of A18 hnRNP are more sensitive to UV radiation. These data suggest that A18 hnRNP plays a protective role against genotoxic stresses by translocating to the cytosol and stabilizing specific transcripts involved in cell survival.
Yang
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C
Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, 108 N. Greene St., Baltimore, MD 21201-1503, USA.
Carrier
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F
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D015152:Blotting, Northern; D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D002467:Cell Nucleus / Q000528:radiation effects; D002470:Cell Survival; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D003593:Cytoplasm / Q000528:radiation effects; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D016366:Open Reading Frames; D010957:Plasmids / Q000378:metabolism; D011061:Poly A; D014176:Protein Biosynthesis; D021381:Protein Transport / Q000528:radiation effects; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D051716:Replication Protein A; D012261:Ribonucleoproteins / Q000737:chemistry* / Q000502:physiology*; D013312:Stress, Physiological; D013997:Time Factors; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C497167:RPA1 protein, human; D011993:Recombinant Fusion Proteins; D051716:Replication Protein A; D012261:Ribonucleoproteins; D011061:Poly A; D015500:Chloramphenicol O-Acetyltransferase