RNA anchoring of Upf1 facilitates recruitment of Dcp2 in the NMD decapping complex.

Upf1 RNA helicase is a pivotal factor in the conserved nonsense-mediated mRNA decay (NMD) process. Upf1 is responsible for coordinating the recognition of premature termination codons (PTCs) in a translation-dependent manner and subsequently triggering mRNA degradation. Multiple factors assist Upf1 during these two consecutive steps. In Saccharomyces cerevisiae, Upf2 and ...
Upf3 associated with Upf1 (Upf1-2/3) contribute to PTC recognition but are absent from the Upf1-decapping complex that includes Nmd4, Ebs1, Dcp1, and Dcp2. Despite their importance for NMD, the organization and dynamics of these Upf1-containing complexes remain unclear. Using recombinant proteins, here we show how distinct domains of Upf1 make direct contacts with Dcp1/Dcp2, Nmd4, and Ebs1. These proteins also bind to each other, forming an extended network of interactions within the Upf1-decapping complex. Dcp2 and Upf2 compete for the same binding site on the N-terminal CH domain of Upf1, which explains the presence of two mutually exclusive Upf1-containing complexes in cells. Our data demonstrate that Nmd4-assisted recruitment of Upf1 promotes anchoring of the decapping enzyme to NMD targets.
Mesh Terms:
Binding Sites, Endoribonucleases, Nonsense Mediated mRNA Decay, Protein Binding, RNA Helicases, RNA, Messenger, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins
Nucleic Acids Res
Date: Feb. 27, 2025
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