Intrinsically disordered regions in eukaryotic mRNA decay pathways.

RNA‐Binding Proteins: Function, Biological Mechanisms, and Therapeutic Opportunities

ABSTRACT RNA‐binding proteins (RBPs) are central regulators of post‑transcriptional gene expression, controlling RNA stability, localization, translation, and alternative splicing. Their functions arise not only from intrinsic RNA‐binding domains but also from dynamic interactions with noncoding RNAs, metabolites, cofactors, and other RBPs. Here, we summarize the structural diversity and core biological activities of canonical and noncanonical RBPs, and delineate how competitive and cooperative regulatory networks dictate RBP function in disease, with an emphasis on cancer. Competitive mechanisms, including lncRNA‐mediated sequestration, antagonistic crosstalk between miRNAs and RBPs, and competition among RBPs for shared substrates, can redirect RNA fate. In contrast, cooperative mechanisms assemble multimolecular ribonucleoprotein complexes that reinforce oncogenic or tumor‐suppressive programs. Dysregulation of these networks promotes proliferation, metastasis, immune evasion, and therapy resistance. We also review emerging therapeutic strategies that target RBP‐centered regulatory circuits, including antisense oligonucleotides, small molecules, protein degraders, and natural products, and we evaluate representative preclinical studies and clinical trials. By integrating mechanistic principles with translational evidence, this review provides a network‐based framework for exploiting RBPs as therapeutic vulnerabilities and for advancing next‐generation precision oncology.

Beyond the structure-function paradigm: A comprehensive review of intrinsically disordered proteins

A cross-kingdom synthesis of disorder-based chromatin regulation is developed, demonstrating that bacterial nucleoid-associated proteins, plant transcription factors, and mammalian chromatin regulators share a conserved charge-regulatory logic, mediated by PTM-dependent mechanisms that dynamically couple environmental signals with genome organization.

Bacterial small regulatory RNAs.

Experimental and Computational Approaches to Identify RNA–Protein Interactions

RNA-binding proteins (RBPs) are essential regulators of RNA metabolism and gene expression, influencing processes such as splicing, stability, localization, and translation. Despite their critical roles in health and disease, including cancer, identifying RNA–protein interactions remains challenging due to technical limitations and biases of existing methods. Here we review and compare experimental techniques—including in vitro affinity purification, in vivo crosslinking, and proximity labeling—and computational prediction tools for RBP identification. We assess their strengths, limitations, and applicability across biological contexts, emphasizing the benefits of integrating experimental and computational strategies. Our analysis provides practical guidelines for selecting appropriate methodologies tailored to different cell types and research goals. These insights aim to facilitate more accurate mapping of RNA–protein interactomes, thereby advancing understanding of RBP functions and supporting the development of novel therapeutic interventions targeting RNA–protein complexes.

Annual Review of Cell and Developmental Biology mRNA-Scaffolded Cytoplasmic Compartments

Bioinformatic pipeline to identify candidate mRNA transcripts targeted by the putative Regulated Ire1-Dependent Decay pathway of Dictyostelium discoideum .

Inositol-requiring protein 1 (Ire1) is a eukaryotic stress sensor that counteracts the buildup of unfolded proteins in the endoplasmic reticulum (ER) by activating the Unfolded Protein Response (UPR) via a specific ribonuclease (RNase) activity. The amoeba Dictyostelium discoideum relies on an ire1 ortholog, ireA , to survive ER stress, but the mRNA transcripts targeted by the IreA ribonuclease remain unknown. In this work, we developed a bioinformatic pipeline that identified 21 mRNA transcripts of D. discoideum that contain a consensus Ire1 cut site found within a secondary mRNA hairpin loop structure and have the potential to be cut by IreA.