Functions in the interphase cytoplasm are less understood. Here, we identify a requirement for poly(ADP-ribose) in the assembly of cytoplasmic stress granules, which accumulate RNA-binding proteins that regulate the translation and stability of mRNAs upon stress.
We show that poly(ADP-ribose), six specific poly(ADP-ribose) polymerases, and two poly(ADP-ribose) glycohydrolase isoforms are stress granule components. A subset of stress granule proteins, including microRNA-binding Argonaute family members Ago1-4, are modified by poly(ADP-ribose), and such modification increases upon stress, a condition when both microRNA-mediated translational repression and microRNA-directed mRNA cleavage are relieved.
Similar relief of repression is also observed upon overexpression of specific poly(ADP-ribose) polymerases or, conversely, upon knockdown of glycohydrolase.
We conclude that poly(ADP-ribose) is a key regulator of posttranscriptional gene expression in the cytoplasm.