Nuclear deadenylation/polyadenylation factors regulate 3′ processing in response to DNA damage

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Abstract
We previously showed that mRNA 3′ end cleavage reaction in cell extracts is strongly but transiently inhibited under DNA‐damaging conditions. The cleavage stimulation factor‐50 (CstF‐50) has a role in this response, providing a link between transcription‐coupled RNA processing and DNA repair. In this study, we show that CstF‐50 interacts with nuclear poly(A)‐specific ribonuclease (PARN) using in vitro and in extracts of UV‐exposed cells. The CstF‐50/PARN complex formation has a role in the inhibition of 3′ cleavage and activation of deadenylation upon DNA damage. Extending these results, we found that the tumour suppressor BARD1, which is involved in the UV‐induced inhibition of 3′ cleavage, strongly activates deadenylation by PARN in the presence of CstF‐50, and that CstF‐50/BARD1 can revert the cap‐binding protein‐80 (CBP80)‐mediated inhibition of PARN activity. We also provide evidence that PARN along with the CstF/BARD1 complex participates in the regulation of endogenous transcripts under DNA‐damaging conditions. We speculate that the interplay between polyadenylation, deadenylation and tumour‐suppressor factors might prevent the expression of prematurely terminated messengers, contributing to control of gene expression under different cellular conditions.