A nuclear export block triggers the decay of newly synthesized polyadenylated RNA
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A nuclear export block triggers the decay of newly synthesized polyadenylated RNA Agnieszka Tudek1, Manfred Schmid1, Marius Makaras1, J. David Barrass2, Jean D. Beggs2, Torben Heick Jensen1* 1Department of Molecular Biology and Genetics, Aarhus University, C. F. Møllers Allé 3, building 1130, 8000 Aarhus C, Denmark, 2Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, UK *corresponding author and lead contact: thj@mbg.au.dk Keywords: nuclear export of pA+ RNA, nuclear degradation of pA+ RNA, Mex67p, Nab2p, transcription. ABSTRACT Genomes are promiscuously transcribed necessitating mechanisms that facilitate the sorting of RNA for function or destruction. The polyA (pA) tail is one such distinguishing feature, which in the Saccharomyces cerevisiae nucleus is bound by the Nab2p protein, yielding transcript protection. As Nab2p also contacts the main nuclear export factor Mex67p, we asked whether transport kinetics contributes to RNA sorting. Indeed, 3’end sequencing of newly transcribed pA+ RNAs demonstrates that nuclear depletion of Mex67p elicits their instant and global decay. A similar phenotype is evident upon inactivation of other export factors and proportional to the amount of nuclear pA+ RNA. As RNA expression is partially rescued by Nab2p over-expression, we propose that an export-block out-titrates Nab2p onto nuclear retained pA+ RNA, reducing the pool of Nab2p available to protect new transcripts. More generally, we suggest that nuclear RNA decay, negotiated by Nab2p availability, aids in balancing cellular transcript supply with demand.
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