A Nuclear Export Block Triggers the Decay of Newly Synthesized Polyadenylated RNA

Agnieszka Tudek, Manfred Schmid, Marius Makaras, J. David Barrass, Jean D. Beggs, Torben Heick Jensen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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 overexpression, 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. Tudek et al. show that nuclear accumulation of existing pA+ RNA, due to an export block, results in the out-titration of the pA-binding protein Nab2p away from newly synthesized pA+ RNAs. The absence of Nab2p results in transcript decay, which highlights the importance of efficient nuclear export for mRNA stability.

Original languageEnglish
Pages (from-to)2457-2467.e7
JournalCell Reports
Volume24
Issue number9
DOIs
Publication statusPublished - 28 Aug 2018

Keywords / Materials (for Non-textual outputs)

  • Mex67p
  • Nab2p
  • nuclear degradation of pA RNA
  • nuclear export of pA RNA
  • transcription

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