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iCLIP - Transcriptome-wide Mapping of Protein-RNA Interactions with Individual Nucleotide Resolution
Published on: April 30, 2011
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Widespread autogenous mRNA-protein interactions detected by CLIP-seq
Thomas H Kapral1,2, Fiona Farnhammer1,3,4, Weihao Zhao5
1Departmet of Structural and Computational Biology, Max Perutz Labs, University of Vienna, Vienna, A-1030, Austria.
Nucleic Acids Research
|September 15, 2022
Summary
RNA-binding proteins (RBPs) commonly interact with their own mRNAs, a widespread phenomenon across organisms. This autogenous interaction, favored by intrinsic affinities, plays a key role in cellular regulation.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Autogenous interactions between mRNAs and encoded proteins are suggested in cellular feedback regulation but lack clear mechanistic understanding.
- A hypothesis posits these interactions are common, influenced by inherent nucleobase-amino acid affinities shaping the genetic code.
- The full extent and mechanisms of these autogenous interactions remain largely undefined.
Purpose of the Study:
- To comprehensively analyze the prevalence and significance of autogenous interactions between RNA-binding proteins (RBPs) and their own mRNAs.
- To investigate the mechanistic underpinnings and statistical validity of these interactions, considering various confounding factors.
- To explore the relationship between intrinsic nucleobase-amino acid affinities and autogenous binding patterns.
Main Methods:
- Analysis of a large dataset from multiple CLIP-seq experiments across diverse organisms.
- Statistical validation using null distributions to assess the significance of observed interactions.
- Investigation of factors influencing autogenous binding, including RBP motifs, structured domains, and experimental variables.
Main Results:
- Widespread autogenous interactions were observed, with 67% of studied RBPs interacting with their own mRNAs.
- Interactions showed enrichment among high-confidence hits and a preference for binding within coding sequences.
- Statistical analysis confirmed the high significance of these autogenous interactions, independent of confounding factors.
Conclusions:
- Autogenous interactions between RBPs and their mRNAs are a prevalent regulatory mechanism across species.
- Intrinsic nucleobase-amino acid affinities likely contribute to the observed co-aligned binding patterns.
- These findings suggest a fundamental link between genetic coding and protein-RNA binding in cellular regulation.
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