title: Nonsense-associated altered splicing: a frame-dependent response distinct from nonsense-mediated decay.
abstract: Nonsense-associated altered splicing (NAS) is a putative correction response that upregulates alternatively spliced transcripts that have skipped offending premature termination codons (PTCs). Here, we examined whether NAS has characteristics in common with nonsense-mediated decay (NMD), a surveillance mechanism that degrades PTC-bearing mRNAs. We discovered that although NAS shared the need for a Kozak AUG to define frame, it differed from NMD. NAS was not affected by depletion of the NMD protein hUPF2, and it functioned independently of RNA stabilization. We identified an alternatively spliced transcript acted upon by both NAS and NMD, indicating that these two mechanisms are not mutually exclusive. Our results suggest that NAS and NMD are distinct mechanisms despite being triggered by the same signal.
authors.affiliation: Department of Immunology, The University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Yao Fu
authors.initials: YF
authors.lastname: Chang
authors.forename: John I
authors.initials: JI
authors.lastname: Hamilton
authors.forename: Miles F
authors.initials: MF
authors.lastname: Wilkinson
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D001483:Base Sequence; D018389:Codon, Nonsense / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D009154:Mutation; D014176:Protein Biosynthesis; D020871:RNA Stability; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016364:Reading Frames / Q000235:genetics*; D013997:Time Factors
chemical_list: D018389:Codon, Nonsense; D012333:RNA, Messenger