Intranuclear degradation of nonsense codon-containing mRNA.
Most vertebrate mRNAs with premature termination codons (PTCs) are specifically recognized and degraded by a process referred to as nonsense-mediated mRNA decay (NMD) while still associated with the nucleus. However, it is still a matter of debate whether PTCs can be identified by intranuclear scanning or only by ribosomes on the cytoplasmic side of the nuclear envelope. Here we show that inhibition of mRNA export by two independent approaches does not affect the downregulation of PTC-containing T-cell receptor beta transcripts in the nuclear fraction of mammalian cells, providing strong evidence for intranuclear NMD. Our results are fully consistent with recently reported evidence for nuclear translation and suggest that an important biological role for nuclear ribosomes is the early elimination of nonsense mRNA during a pioneer round of translation.
Bühler
Marc
M
Institute of Cell Biology, University of Bern, Baltzerstrasse-4, Switzerland.
Wilkinson
Miles F
MF
Mühlemann
Oliver
O
D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D018389:Codon, Nonsense; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D009865:Oocytes / Q000502:physiology; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism; D014982:Xenopus laevis
D018389:Codon, Nonsense; D008164:Luminescent Proteins; C094460:M protein, Vesicular stomatitis virus; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins; D049452:Green Fluorescent Proteins