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Related Experiment Video

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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

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A Conserved 3'UTR Stem-loop Directs UPF1/eIF4AIII-Dependent Regulation of GABARAPL1 mRNA.

Chloé Mercier¹, Maëlys Baudin², Francesca Fiorini²

¹Université Marie et Louis Pasteur, EFS INSERM UMR1098 RIGHT, F-25000 Besançon, France.

Journal of Molecular Biology

|May 10, 2026

Summary

Researchers identified a novel RNA element in the GABARAPL1 3'UTR that regulates gene expression. This element binds RNA helicases UPF1 and eIF4AIII, revealing an EJC-independent mechanism for nonsense-mediated mRNA decay (NMD).

Keywords:

3′UTR GABARAPL1 UPF1 eIF4AIII stem-loop

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Area of Science:

Molecular Biology
RNA Biology
Gene Regulation

Background:

RNA-binding proteins (RBPs) regulate mRNA fate through interactions with untranslated regions.
Nonsense-mediated mRNA decay (NMD) is a key pathway for degrading aberrant mRNAs, often involving exon-junction complexes (EJCs).
EJC-independent NMD mechanisms, particularly those involving 3'UTRs, are less understood.

Purpose of the Study:

To elucidate the molecular mechanism by which the GABARAPL1 3'UTR targets mRNA for NMD.
To identify cis-regulatory elements within the GABARAPL1 3'UTR involved in UPF1-dependent regulation.
To characterize the interaction of UPF1 and eIF4AIII with the GABARAPL1 3'UTR.

Main Methods:

Investigated GABARAPL1 regulation using chemical inhibition of eIF4AIII.
Identified a conserved RNA region (nucleotides 364-421) in the GABARAPL1 3'UTR.
Employed biochemical analyses (protein binding, secondary structure analysis) and molecular modeling.

Main Results:

GABARAPL1 is regulated via an EJC-independent mechanism involving its 3'UTR.
A specific conserved RNA region (364-421) within the GABARAPL1 3'UTR was identified as crucial for targeting.
UPF1 and eIF4AIII directly bind to this RNA region, which exhibits a stable structure with local flexibility.

Conclusions:

UPF1 and eIF4AIII act as specific regulators of GABARAPL1 transcripts.
A novel RNA regulatory element in the GABARAPL1 3'UTR provides an unexpected binding site for UPF1 and eIF4AIII.
This discovery sheds light on EJC-independent NMD pathways and RNA-protein interactions.