title: Co-transcriptional degradation of aberrant pre-mRNA by Xrn2.
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.
authors.affiliation: Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK.
authors.forename: Lee
authors.initials: L
authors.lastname: Davidson
authors.forename: Alastair
authors.initials: A
authors.lastname: Kerr
authors.forename: Steven
authors.initials: S
authors.lastname: West
mesh_terms: D005095:Exoribonucleases / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D011714:Pyrans / Q000378:metabolism; D012322:RNA Precursors / Q000378:metabolism*; D012326:RNA Splicing; D020871:RNA Stability; D013141:Spiro Compounds / Q000378:metabolism; D014158:Transcription, Genetic; D055544:beta-Globins / Q000096:biosynthesis
chemical_list: D011714:Pyrans; D012322:RNA Precursors; D013141:Spiro Compounds; D055544:beta-Globins; C553684:spliceostatin A; D005095:Exoribonucleases; C120903:XRN2 protein, human