Structural basis of long non-coding RNA PVT1 interactions with select mRNAs universal in pan-cancer system: A...

Area of Science:

• Molecular Biology
• Genetics
• Bioinformatics

Background:

• PVT1 lncRNA regulates gene expression through mRNA binding.
• Previous studies predicted PVT1-mRNA interactions in pan-cancer systems.
• The structural basis of these interactions remains unclear.

Purpose of the Study:

• Identify and compare secondary structural features mediating PVT1 binding to cancer-relevant mRNAs.
• Determine the evolutionary conservation of these structural interactions.
• Elucidate the mechanism of PVT1-mRNA complex formation.

Main Methods:

• Secondary structure folding analysis to identify intermolecular interactions.
• Covariation analysis to detect conserved structural elements.
• Analysis of base composition and GC content in lncRNA-mRNA interaction regions.

Main Results:

• PVT1 forms stable secondary structures with mRNAs using Watson-Crick and non-Watson-Crick base pairs.
• Covariation analysis revealed 10 conserved base pairs in PVT1, indicating structural conservation.
• Interactions predominantly occur in open loop regions, with a higher A-U nucleotide content in PVT1 loops.
• Some mRNAs exhibit stable secondary structures due to higher GC content, particularly in CDS and 3'UTR regions.
• A mechanism for PVT1 binding to multiple mRNAs simultaneously or sequentially was proposed.

Conclusions:

• PVT1's secondary structure flexibility facilitates binding to diverse mRNA regions.
• Conserved structural elements in PVT1 suggest functional importance.
• The study provides insights into PVT1-mRNA interaction mechanisms and their role in gene regulation.
• PVT1 may regulate multiple mRNAs through spatio-temporal binding.