The UV-inducible RNA-binding Protein A18 (A18 hnRNP) Plays a Protective Role in the Genotoxic Stress Response

Chonglin Yang, France Carrier
2001 Journal of Biological Chemistry  
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,
more » ... were identified, most of which are stress-or UVresponsive 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 man- ner. 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. EXPERIMENTAL PROCEDURES Plasmids-To express A18 hnRNP in mammalian cells, the open reading frame (ORF) of A18 hnRNP cDNA was cloned into the HindIII/
doi:10.1074/jbc.m105396200 pmid:11574538 fatcat:oa24uzyt6va7tfyujpmlpyhtny