Challenges in Therapeutically Targeting the RNA‐Recognition Motif DOI Creative Commons
Stefan Schmeing, Peter ‘t Hart

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2024, Volume and Issue: 15(6)

Published: Nov. 1, 2024

ABSTRACT The RNA recognition motif (RRM) is the most common binding domain found in human proteome. RRM domains provide RNA‐binding proteins with sequence specific allowing them to participate RNA‐centric processes such as mRNA maturation, translation initiation, splicing, and degradation. They are drivers of various diseases through overexpression or mutation, making attractive therapeutic targets addressing these their chemical compounds gaining ever more attention. However, it still very challenging find selective potent RNA‐competitors due small size high structural conservation its interface. Despite challenges, a selection has been reported for several containing proteins, but often limited biophysical evidence low selectivity. A solution selectively targeting might be avoiding surface altogether, rather look composite pockets formed other protein–protein interaction sites that regulate target's activity less conserved. Alternative modalities, oligonucleotides, peptides, molecular glues, exciting new approaches address achieve goal intervention at regulatory level.

Language: Английский

RNA BINDING PROTEINS (RBPs) ON GENETIC STABILITY AND DISEASES DOI Creative Commons
Abdullahi Tunde Aborode, Ohilebo Abdulateef Abass,

Shaibu Nasiru

et al.

Global Medical Genetics, Journal Year: 2025, Volume and Issue: 12(1), P. 100032 - 100032

Published: Jan. 21, 2025

RNA-binding proteins (RBPs) are integral components of cellular machinery, playing crucial roles in the regulation gene expression and maintaining genetic stability. Their interactions with RNA molecules govern critical processes such as mRNA splicing, stability, localization, translation, which essential for proper function. These interact other to form ribonucleoprotein complexes (RNPs), hence controlling fate target RNAs. The interaction occurs via recognition motif, zinc finger domain, KH domain double stranded binding motif (all known domains (RBDs). found within coding sequences (intron exon domains), 5' untranslated regions (5'UTR) 3' (3'UTR). Dysregulation RBPs can lead genomic instability, contributing various pathologies, including cancer neurodegenerative diseases, metabolic disorders. This study comprehensively explores multifaceted highlighting their involvement integrity through modulation processing implications signalling pathways. Furthermore, it discusses how aberrant RBP function precipitate instability disease progression, emphasizing therapeutic potential targeting restoring homeostasis. Through an analysis current literature, this aims delineate role ensuring stability promise targets innovative strategies.

Language: Английский

Citations

0
Musashi inhibitor Ro 08–2750 attenuates triple-negative breast cancer cell proliferation and migration and acts as a novel chemo- and radiosensitizer DOI

Kathrin A. Brücksken,

Mark Sicking,

Eberhard Korsching

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 186, P. 118002 - 118002

Published: March 22, 2025

Language: Английский

Citations

0
Challenges in Therapeutically Targeting the RNA‐Recognition Motif DOI Creative Commons
Stefan Schmeing, Peter ‘t Hart

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2024, Volume and Issue: 15(6)

Published: Nov. 1, 2024

ABSTRACT The RNA recognition motif (RRM) is the most common binding domain found in human proteome. RRM domains provide RNA‐binding proteins with sequence specific allowing them to participate RNA‐centric processes such as mRNA maturation, translation initiation, splicing, and degradation. They are drivers of various diseases through overexpression or mutation, making attractive therapeutic targets addressing these their chemical compounds gaining ever more attention. However, it still very challenging find selective potent RNA‐competitors due small size high structural conservation its interface. Despite challenges, a selection has been reported for several containing proteins, but often limited biophysical evidence low selectivity. A solution selectively targeting might be avoiding surface altogether, rather look composite pockets formed other protein–protein interaction sites that regulate target's activity less conserved. Alternative modalities, oligonucleotides, peptides, molecular glues, exciting new approaches address achieve goal intervention at regulatory level.

Language: Английский

Citations

0