The Role of the Human Nuclear Poly(A) Binding Protein in RNA Decay




Bresson, Stefan

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Control of nuclear RNA stability is an important determinant of gene expression, but the factors involved in nuclear RNA decay remain largely unknown in higher eukaryotes. Here, I describe our work showing that polyadenosine (poly(A)) tails can stimulate transcript decay in the nucleus of human cells, a function mediated by the ubiquitous nuclear poly(A) binding protein PABPN1. We show that PABPN1 is required for the degradation of a viral nuclear noncoding RNA as well as an inefficiently exported human mRNA. Importantly, the targeting of RNAs to this decay pathway requires the PABPN1 and poly(A) polymerase (PAP)-dependent extension of the poly(A) tail. Nuclear transcripts with longer poly(A) tails are then selectively degraded by components of the nuclear exosome. I also describe our work showing that PABPN1 and PAP are required for the degradation of a variety of nuclear-retained long noncoding RNAs. Taken together, this work uncovers an important pathway in the turnover of RNAs in the nucleus.

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