Most eukaryotic mRNAs are polyadenylated in the nucleus, and the
poly(A)-tail is required for efficient
mRNA export and translation. However, mechanisms governing
mRNA transport remain unclear. Here, we report that the
nicotinamide adenine dinucleotide (
NAD)-dependent deacetylase
SIRT1 acts as an energy sensor and negatively regulates
poly(A)RNA transport via deacetylating a
poly(A)-binding protein, PABP1. Upon energy
starvation,
SIRT1 interacts with and deacetylates PABP1 and deactivates its
poly(A)RNA binding, leading to nuclear accumulation of PABP1 and
poly(A)RNA and thus facilitating eukaryotic cells to attenuate
protein synthesis and energy consumption to adapt to energy stress. Moreover, AMPK-directed
SIRT1 phosphorylation is required for energy
starvation-induced PABP1-SIRT1 association, PABP1 deacetylation, and
poly(A)RNA nuclear retention. In addition, the SIRT1-PABP1 association is not specific to energy
starvation but represents a common stress response. These observations provide insights into dynamic modulation of eukaryotic
mRNA transport and translation, suggesting that the
poly(A)-tail also provides a basis for eukaryotes to effectively shut down mature
mRNA transport and thereby tailor
protein synthesis to maintain energy homeostasis under stress conditions.