Nuclear deadenylation/polyadenylation factors regulate 3' processing in response to DNA damage.
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.
Cevher
Murat A
MA
Department of Chemistry, Hunter College, City University of New York, New York, NY, USA.
Zhang
Xiaokan
X
Fernandez
Sully
S
Kim
Sergey
S
Baquero
Jorge
J
Nilsson
Per
P
Lee
Sean
S
Virtanen
Anders
A
Kleiman
Frida E
FE
D002467:Cell Nucleus / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D005095:Exoribonucleases / Q000378:metabolism; D005786:Gene Expression Regulation; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D026723:Polyadenylation; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D014466:Ultraviolet Rays; D039221:mRNA Cleavage and Polyadenylation Factors / Q000378:metabolism*
D005095:Exoribonucleases; D005982:Glutathione Transferase; D012313:RNA; D012333:RNA, Messenger; D011994:Recombinant Proteins; D039221:mRNA Cleavage and Polyadenylation Factors