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Updated: Dec 31, 2025

Detection of RNA-binding Proteins by In Vitro RNA Pull-down in Adipocyte Culture
Published on: July 22, 2016
Human protein-RNA interaction network is highly stable across mammals
Aarthi Ramakrishnan1, Sarath Chandra Janga2,3,4
1Department of Biohealth Informatics, School of Informatics and Computing, Indiana University Purdue University, Indianapolis, IN, 46202, USA.
RNA-binding protein (RBP) binding sites are highly conserved across primates, with conserved RBP-RNA interactions suggesting importance in vertebrate evolution. RBP expression and target number influence binding site conservation, particularly in 3' gene regions.
Area of Science:
- Genomics
- Molecular Biology
- Evolutionary Biology
Background:
- RNA-binding proteins (RBPs) regulate RNA metabolism and RBP-RNA interactions in eukaryotes.
- Previous studies on RBP target conservation focused on lower eukaryotes, leaving mammalian conservation less understood.
Purpose of the Study:
- To investigate the conservation of RNA-binding protein (RBP) binding sites across mammalian species.
- To identify factors influencing the conservation patterns of RBP binding sites.
Main Methods:
- Utilized CLIP-seq datasets for 60 human RBPs.
- Performed comparative analysis of RBP binding site conservation across vertebrate species.
- Conducted multivariate analysis to identify contributing factors to conservation differences.
- Examined binding site locations at the gene level (e.g., 3' regions).
- Performed gene set enrichment analysis for phenotype associations.
Main Results:
- Most binding sites for a third of studied RBPs are conserved in at least 50% of vertebrate species.
- RBP binding sites show median conservation of 58%, significantly higher than random genomic locations.
- Binding sites are highly conserved in primates, with weaker conservation in birds and fishes.
- RBP expression level and number of post-transcriptional targets are key factors in conservation extent.
- Binding sites in 3' gene regions are highly conserved (90% of RBPs show higher conservation here than in 5' regions).
- Enrichment for developmental abnormalities was found when analyzing conserved binding sites.
Conclusions:
- Human RBP binding sites are highly conserved in primates, with weaker conservation in lower vertebrates.
- Phylogenetic relationships do not explain RBP binding site conservation patterns.
- RBP expression and target number significantly impact binding site conservation.
- 3' gene regions represent the most conserved locations for RBP binding sites.
- Conserved binding sites highlight the role of developmental events in post-transcriptional regulatory network evolution.
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