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Structure-Mediated RNA Decay by UPF1 and G3BP1
Joseph W Fischer1, Veronica F Busa1, Yue Shao2
1McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
Molecular Cell
|February 5, 2020
Summary
Cells use RNA structure in the 3' untranslated region (UTR) to control RNA levels. This structure-based decay pathway, involving UPF1 and G3BP1 proteins, regulates both coding and noncoding RNAs.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Post-transcriptional regulation is crucial for controlling gene expression.
- The 3' untranslated region (UTR) of messenger RNAs (mRNAs) plays a significant role in RNA stability and decay.
- Specific sequence features in the 3' UTR often target mRNAs for degradation.
Purpose of the Study:
- To characterize a genome-wide RNA decay pathway regulated by the overall structure of the 3' UTR.
- To investigate the mechanism of structure-mediated RNA decay, independent of specific single-stranded sequences.
- To identify the key proteins involved in this novel decay pathway.
Main Methods:
- Analysis of RNA decay rates based on 3' UTR structural complexity.
- Experimental manipulation of 3' UTR structure through fusions and mutations.
- Assessment of RNA levels upon depletion of specific RNA-binding proteins (UPF1 and G3BP1).
Main Results:
- A novel RNA decay pathway was identified, dependent on the overall base-paired structure of the 3' UTR.
- This structure-mediated regulation is maintained regardless of sequence orientation and can be disrupted by altering 3' UTR structure.
- Depletion of UPF1 or G3BP1 led to increased levels of mRNAs and circular RNAs with highly structured 3' UTRs.
Conclusions:
- Cells possess a mechanism to selectively regulate coding and noncoding RNAs based on 3' UTR structural properties.
- The RNA-binding proteins UPF1 and G3BP1 are essential components of this structure-dependent RNA decay pathway.
- This finding reveals a new layer of post-transcriptional control governing RNA stability and expression.