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Identification and targeting of G-quadruplex structures in MALAT1 long non-coding RNA
Xi Mou1, Shiau Wei Liew1, Chun Kit Kwok1,2
1Department of Chemistry and State Key Laboratory of Marine Pollution, City University of Hong Kong, Kowloon Tong, Hong Kong SAR, China.
Nucleic Acids Research
|December 14, 2021
Summary
This study reveals RNA G-quadruplexes (rG4s) in MALAT1 long non-coding RNA (lncRNA) that bind NONO protein. These rG4s can be targeted by small molecules, peptides, and aptamers to disrupt the interaction.
Area of Science:
- Molecular Biology
- RNA Biology
- Genomics
Background:
- RNA G-quadruplexes (rG4s) are increasingly recognized for their functional roles in cellular processes.
- While studied in coding RNAs, rG4s in non-coding RNAs (ncRNAs), particularly long non-coding RNAs (lncRNAs), remain underexplored.
- lncRNAs are significant in biological functions and disease, making their structural and functional characterization crucial.
Purpose of the Study:
- To investigate the presence and structure of rG4s within the MALAT1 lncRNA.
- To determine if MALAT1 rG4s interact with the NONO protein.
- To explore therapeutic strategies targeting MALAT1 rG4s and their associated protein complexes.
Main Methods:
- Bioinformatic analysis to identify conserved rG4 motifs in MALAT1.
- Structural analysis to confirm thermostable parallel rG4 formation.
- In vitro and cellular assays to assess MALAT1 rG4 interaction with NONO protein.
- Experiments using small molecules, peptides, and aptamers to target MALAT1 rG4s.
Main Results:
- Conserved, thermostable, parallel rG4 structures were identified in MALAT1 lncRNA.
- MALAT1 rG4s specifically and with high affinity interact with NONO protein in vitro and in cell lysates.
- Cellular data confirmed NONO protein recognizes MALAT1 lncRNA through its rG4 motifs.
- rG4-specific agents (small molecule, peptide, L-aptamer) successfully disrupted the MALAT1 rG4-NONO interaction.
Conclusions:
- This study identifies novel rG4s in MALAT1 lncRNA, highlighting their significance beyond coding RNAs.
- The specific interaction between MALAT1 rG4s and NONO protein is characterized, revealing a new RNA-protein interaction mechanism.
- Targeting MALAT1 rG4s presents a viable strategy for modulating MALAT1 function and its complexes, with therapeutic potential.
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