RNA-binding protein Musashi homolog 1 (Musashi-1) (MSI1)

RNA-binding protein Musashi homolog 1 (MSI1) is a highly conserved protein that serves as a master regulator of post-transcriptional gene expression, primarily in stem and progenitor cells (UniProt P51843). It functions by binding to specific motifs in the 3' untranslated regions (UTRs) of target mRNAs, such as Numb and p21, to repress their translation and thereby maintain the self-renewal capacity and pluripotency of stem cells (PubMed PMID: 28655771). In the context of human disease, MSI1 is frequently upregulated in various malignancies, including glioblastoma, colorectal, and breast cancer, where it drives tumor progression, metastasis, and chemoresistance by activating the Notch and Wnt signaling pathways (PubMed PMID: 30104347). Beyond oncology, MSI1 has been implicated in neurodegenerative diseases and the replication of certain viruses, such as the Zika virus (PubMed PMID: 27512084). As a therapeutic target, MSI1 is being addressed through the development of small molecule inhibitors like Ro 08-2750, which aim to disrupt its RNA-binding domain and restore the expression of tumor suppressors (PubMed PMID: 24510544). However, therapeutic development must carefully consider the potential impact on normal stem cell populations in the brain and gastrointestinal tract.

Other names

MSI1Musashi-1Musashi homolog 1MSI1H

Inhibition of the RNA-binding activity of the RNA recognition motif 1 (RRM1) domain, preventing the sequestration and translational repression of target mRNAs such as Numb and CDKN1A, which subsequently modulates oncogenic pathways like Notch and Wnt (PubMed PMID: 24510544).