Co-transcriptional degradation of aberrant pre-mRNA by Xrn2

Lee Davidson, Alastair Kerr, Steven West

Research output: Contribution to journalArticlepeer-review

Abstract

Eukaryotic protein-coding genes are transcribed as pre-mRNAs that are matured by capping, splicing and cleavage and polyadenylation. Although human pre-mRNAs can be long and complex, containing multiple introns and many alternative processing sites, they are usually processed co-transcriptionally. Mistakes during nuclear mRNA maturation could lead to potentially harmful transcripts that are important to eliminate. However, the processes of human pre-mRNA degradation are not well characterised in the human nucleus. We have studied how aberrantly processed pre-mRNAs are degraded and find a role for the 5'→3' exonuclease, Xrn2. Xrn2 associates with and co-transcriptionally degrades nascent β-globin transcripts, mutated to inhibit splicing or 3' end processing. Importantly, we provide evidence that many endogenous pre-mRNAs are also co-transcriptionally degraded by Xrn2 when their processing is inhibited by Spliceostatin A. Our data therefore establish a previously unknown function for Xrn2 and an important further aspect of pre-mRNA metabolism that occurs co-transcriptionally.
Original languageEnglish
Pages (from-to)2566-2578
Number of pages13
JournalEMBO Journal
Volume31
Issue number11
Early online date20 Apr 2012
DOIs
Publication statusPublished - 2012

Keywords

  • transcription
  • RNA processing
  • RNA degradation

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