Posttranscriptional gene regulation by spatial rearrangement of the 3' untranslated region.
Translation termination at premature termination codons (PTCs) triggers degradation of the aberrant mRNA, but the mechanism by which a termination event is defined as premature is still unclear. Here we show that the physical distance between the termination codon and the poly(A)-binding protein PABPC1 is a crucial determinant for PTC recognition in human cells. "Normal" termination codons can trigger nonsense-mediated mRNA decay (NMD) when this distance is extended; and vice versa, NMD can be suppressed by folding the poly(A) tail into proximity of a PTC or by tethering of PABPC1 nearby a PTC, indicating an evolutionarily conserved function of PABPC1 in promoting correct translation termination and antagonizing activation of NMD. Most importantly, our results demonstrate that spatial rearrangements of the 3' untranslated region can modulate the NMD pathway and thereby provide a novel mechanism for posttranscriptional gene regulation.
Eberle
Andrea B
AB
Institute of Cell Biology, University of Berne, Berne, Switzerland .
Stalder
Lukas
L
Mathys
Hansruedi
H
Orozco
Rodolfo Zamudio
RZ
Mühlemann
Oliver
O
D020413:3' Untranslated Regions / Q000378:metabolism*; D018389:Codon, Nonsense / Q000378:metabolism; D006801:Humans; D011061:Poly A / Q000378:metabolism; D039122:Poly(A)-Binding Protein I / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism
D020413:3' Untranslated Regions; D018389:Codon, Nonsense; D039122:Poly(A)-Binding Protein I; D012333:RNA, Messenger; D011061:Poly A