# Decoding RNA–protein interactions using high-throughput methods

**Authors:** Marianne Régis, Paola Pulcina, Dmitry A. Kretov

PMC · DOI: 10.1080/15476286.2026.2623240 · RNA Biology · 2026-01-28

## TL;DR

This paper reviews high-throughput methods for studying RNA–protein interactions, which are crucial for understanding gene regulation and disease.

## Contribution

The paper provides a comprehensive overview of MPBAs, highlighting their potential for decoding RNA–protein interaction rules.

## Key findings

- MPBAs use RNA or protein variant libraries to study RNA–protein interactions systematically.
- Both in vitro and in vivo MPBA approaches have distinct strengths and limitations.
- Future challenges include improving methods to better decode RNA-binding protein recognition.

## Abstract

RNA-binding proteins (RBPs) constitute a diverse class of proteins essential for every stage of the gene expression process. Many RBPs are also linked to human diseases and pathologies. Understanding the molecular grammar of RNA–protein interactions is critical for deciphering the regulatory RNA code. This review provides a comprehensive overview of Massively Parallel Binding Assays (MPBAs), high-throughput techniques that use large libraries of RNA or protein variants to systematically investigate RNA–protein interactions. We describe the underlying principles of both in vitro and in vivo approaches, their applications, as well as their strengths and weaknesses. We conclude by outlining future directions and challenges in the field that will help drive the development of novel methods to better understand the RBP recognition code.

## Full-text entities

- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12915805/full.md

## References

146 references — full list in the complete paper: https://tomesphere.com/paper/PMC12915805/full.md

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Source: https://tomesphere.com/paper/PMC12915805