Musashi RNA-Binding Proteins in Stem Cell Biology and Cancer

Musashi proteins, comprising Musashi-1 (MSI1) and Musashi-2 (MSI2), are conserved RNA-binding factors that govern post-transcriptional gene regulation in stem and progenitor cells. By recognising a core UAG-containing motif via tandem RNA recognition motifs, they modulate the translation and stability of mRNAs implicated in self-renewal, differentiation and cell fate decisions. In normal tissues, Musashi proteins maintain stem cell pools in the nervous system, intestine and haematopoietic compartments. However, upon dysregulation they assume oncogenic roles by sustaining cancer stem cell phenotypes, enhancing epithelial–mesenchymal transition, promoting therapy resistance and facilitating DNA damage repair. Accumulating evidence positions MSI1 and MSI2 as both biomarkers of tumour aggressiveness and targets for therapeutic intervention across diverse malignancies.

Research from Nature Portfolio

Seminal efforts have demonstrated that direct inhibition of MSI2’s RNA-binding activity can reverse malignant phenotypes in leukaemia models. A selective small molecule was shown to occupy MSI2’s RNA-interaction surface, displace oncogenic transcripts and induce differentiation and apoptosis in acute myeloid leukaemia cells, with concomitant suppression of c-MYC and reduction of disease burden in vivo. In the intestinal epithelium, inducible overexpression of MSI2 revealed its capacity to mimic loss of the APC tumour suppressor, driving adenoma-like changes by repressing multiple tumour-suppressor transcripts and engaging the PDK–AKT–mTORC1 axis. Complementary studies in colorectal carcinoma have established that MSI1 is enriched in CD44+ cancer stem cell subsets, orchestrates the assembly of anti-apoptotic stress granules under chemotoxic stress and underpins chemoresistance via its C-terminal domain.

Musashi RNA-Binding Proteins in Stem Cell Biology and Cancer publication trend

The graph below shows the total number of articles in musashi rna-binding proteins in stem cell biology and cancer across all publications each year (not limited to Nature Index journals).

Technical terms

RNA-binding protein: A protein that binds specific RNA sequences to influence splicing, stability or translation.

RNA recognition motif (RRM): A conserved domain of ~90 amino acids that mediates sequence-specific RNA binding.

Cancer stem cell: A subpopulation within a tumour capable of self-renewal, differentiation and driving tumour growth.

Epithelial–mesenchymal transition (EMT): A process in which epithelial cells acquire mesenchymal traits, enhancing motility and invasiveness.

Stress granule: A cytoplasmic aggregate of stalled translation pre-initiation complexes formed under stress to protect mRNAs.

References

1. The Musashi RNA-binding proteins in female cancers: insights on molecular mechanisms and therapeutic relevance. Biomarker Research (2023).
2. Mechanism of Musashi2 affecting radiosensitivity of lung cancer by modulating DNA damage repair. MedComm (2024).
3. MicroRNA-143 acts as a tumor suppressor through Musashi-2/DLL1/Notch1 and Musashi-2/Snail1/MMPs axes in acute myeloid leukemia. Journal of Translational Medicine (2023).
4. Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia. Nature Communications (2019).
5. Transformation of the intestinal epithelium by the MSI2 RNA-binding protein. Nature Communications (2015).
6. A Conserved Three-nucleotide Core Motif Defines Musashi RNA Binding Specificity*. Journal of Biological Chemistry (2014).
7. Musashi-1 promotes a cancer stem cell lineage and chemoresistance in colorectal cancer cells. Scientific Reports (2017).