대규모-언어-모델의-성-편향-탐지-및-완화

대규모-언어-모델에서-성-편향-찾기와-완화하기

geschlechtsspezifische-verzerrungen-in-großen-sprachmodellen-lokalisieren-und-abmildern

다중-모달-대형-언어-모델의-시각적-환각을-완화하는-pensieve-회고-후-비교

pensieve-wie-der-retrospektive-vergleich-visuelle-halluzinationen-reduziert


The interaction between the yeast Nmd4 protein and the helicase domain of Upf1, a central factor in the nonsense-mediated mRNA decay (NMD) pathway, is mediated by a conserved C-terminal "arm" region of Nmd4 and is important for Upf1's ATPase activity and the degradation of NMD substrates.


coremsg

The nonsense-mediated mRNA decay (NMD) pathway clears eukaryotic cells of mRNAs containing premature termination codons (PTC) or normal stop codons located in specific contexts. It therefore plays an important role in gene expression regulation. The precise molecular mechanism of the NMD pathway has long been considered to differ substantially from yeast to metazoa, despite the involvement of universally conserved factors such as the central ATP-dependent RNA-helicase Upf1. Here we describe the crystal structure of the yeast Upf1 bound to its recently identified but yet uncharacterized partner Nmd4, show that Nmd4 stimulates Upf1 ATPase activity and that this interaction contributes to the elimination of NMD substrates. We also demonstrate that a region of Nmd4 critical for the interaction with Upf1 in yeast is conserved in the metazoan SMG6 protein, another major NMD factor. We show that this conserved region is involved in the interaction of SMG6 with UPF1, and that mutations in this region affect the levels of endogenous human NMD substrates. Our results support the universal conservation of the NMD mechanism in eukaryotes.

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Identification of an evolutionary conserved binding motif responsible for the recruitment of NMD factors to the UPF1 helicase

crystal-structure-of-the-nmd4-upf1-complex-reveals-a-conserved-binding-motif-critical-for-nonsense-mediated-mrna-decay


Crystal Structure of the Nmd4-Upf1 Complex Reveals a Conserved Binding Motif Critical for Nonsense-Mediated mRNA Decay
