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Updated: May 28, 2025
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Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
Published on: April 24, 2021
947
SNORD80-guided 2'-O-methylation stabilizes the lncRNA GAS5 to regulate cellular stress responses
Liang Xu1, Xiao Hong Zhao1, Yuan Yuan Zhang1
1School of Biomedical Sciences and Pharmacy, The University of Newcastle, Newcastle, NSW 2308, Australia.
Summary
The small nucleolar RNA SNORD80 guides methylation to stabilize the long noncoding RNA GAS5. This interaction creates a stress-induced regulatory loop, enhancing GAS5 expression.
Area of Science:
- Molecular Biology
- RNA Biology
- Gene Regulation
Background:
- The long noncoding RNA (lncRNA) GAS5 gene contains introns that host multiple C/D box small nucleolar RNAs (snoRNAs).
- A functional relationship between GAS5 and its hosted snoRNAs, particularly SNORD80, remains largely uncharacterized.
Purpose of the Study:
- To investigate the regulatory and functional relationship between GAS5 and its hosted snoRNAs, focusing on SNORD80.
- To elucidate the role of SNORD80 in the posttranscriptional regulation of GAS5 expression.
Main Methods:
- Analysis of gene expression in response to cellular stress.
- Investigating RNA-RNA interactions and RNA modification (2'-O-methylation).
- Gene knockdown and overexpression studies of SNORD80 and fibrillarin.
Main Results:
- SNORD80 expression parallels GAS5 expression and is co-regulated under cellular stress.
- SNORD80 guides 2'-O-methylation at a specific site on GAS5, enhancing its stability and expression.
- SNORD80-mediated methylation is dependent on fibrillarin, the methyltransferase for box C/D snoRNPs.
Conclusions:
- SNORD80 plays a crucial role in stabilizing GAS5 through guiding 2'-O-methylation.
- A feedforward regulatory loop exists at the GAS5 locus, where SNORD80 stabilizes GAS5 in response to cellular stress.
- This study reveals novel posttranscriptional mechanisms governing lncRNA expression and highlights the interplay between snoRNAs and lncRNAs.
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