RNA structure generates natural cooperativity between single-stranded RNA binding proteins targeting 5' and 3'UTRs

Area of Science:

• Molecular Biology
• Bioinformatics
• Genetics

Background:

• Post-transcriptional regulation involves mRNA binding proteins and miRNAs modulating gene function.
• Combinatorial gene regulation requires communication and cooperativity among RNA binding partners.
• RNA secondary structures can mediate cooperativity between binding partners, influencing binding site accessibility.

Purpose of the Study:

• To propose a quantitative measure for structure-mediated cooperativity in RNA.
• To investigate the prevalence and characteristics of RNA structure-mediated cooperativity.
• To determine the impact of RNA sequence elements on cooperativity.

Main Methods:

• Derivation of a quantitative measure (ΔΔG) for structure-mediated cooperativity.
• Application of the measure to analyze a large dataset of human and Caenorhabditis elegans mRNA sequences.
• Analysis of cooperativity across different binding site configurations (proximal and end-to-end).

Main Results:

• Structure-mediated cooperativity is a generic feature in human and C. elegans mRNAs.
• Cooperativity extends beyond proximal binding sites to include end-to-end configurations (5'UTR and 3'UTR).
• End-to-end cooperativity is primarily determined by untranslated region (UTR) sequences, not coding sequences.

Conclusions:

• RNA secondary structures play a crucial role in mediating cooperativity for combinatorial gene regulation.
• A novel quantitative measure effectively captures structure-mediated cooperativity.
• UTR sequences are key determinants of long-range RNA-protein interactions and cooperativity.