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. Author manuscript; available in PMC: 2011 Dec 2.
Published in final edited form as: Wiley Interdiscip Rev RNA. 2010 May 25;1(1):193–199. doi: 10.1002/wrna.20

FIGURE 3.

FIGURE 3

Schematic diagram of the involvement of 3′-end processing in the mRNA surveillance pathway of genes involved in DNA damage response (DDR). (A) AU-rich elements (ARE)-mediated destabilization prior to DNA damage. Genes involved in the early DDR are rapidly degraded in non-treated cells. The ARE-binding proteins (ARE-BP) AUF1 compete with poly(A) binding protein (PABP) for binding to the poly(A) tail, destabilizing and, possibly, exposing it to deadenylases, such as poly(A)-specific ribonuclease (PARN). Alternatively, other ARE-BP, such as tristetraprolin (TTP) and KH-type splicing regulatory protein (KSRP), recruit the deadenylases Ccr4 and PARN to ARE-mRNAs and initiate deadenylation-dependent degradation of those transcripts via the exosome. (B) ARE-mediated stabilization during the DDR. Following DNA damage, genes involved in DDR are up-regulated. In that scenario, the cellular levels of the ARE-BP HuR are up-regulated and HuR competes with AUF1 for binding to the same ARE region. This competition stabilizes the association of the PABP to the poly(A) tail. Moreover, HuR also competes with the other ARE-BP, such as TTP and KRSP, preventing the recruitment of deadenylases to the ARE-mRNA and the exosomal degradation.