LAUSR

Abstract Most eukaryotic genomes are transcribed pervasively, thereby producing an array of long non-coding RNAs (lncRNAs) in addition to protein-coding mRNAs. A large fraction of these lncRNAs is targeted by polyadenylation-dependent decay via the poly(A)-binding protein nuclear 1 (PABPN1) and the RNA exosome. Yet, how PABPN1 contributes to nuclear RNA surveillance by facilitating lncRNA turnover by the RNA exosome remains largely unclear. Here, we show that PABPN1 is important for the nuclear retention of polyadenylated lncRNAs, such that PABPN1 loss of function allows target lncRNAs to evade nuclear decay, leading to cytoplasmic accumulation. Interestingly, we found that another nuclear PABP, ZC3H14, functions antagonistically to PABPN1 and the poly(A)-tail exosome targeting (PAXT) connection in the control of nuclear lncRNA turnover. Collectively, our findings disclose the critical interplay between two conserved nuclear PABPs, PABPN1 and ZC3H14, in RNA surveillance via the control of nuclear RNA export.