RNA-binding protein Musashi (MSI)

The Musashi (MSI) family, primarily consisting of Musashi-1 (MSI1) and Musashi-2 (MSI2), comprises evolutionarily conserved RNA-binding proteins that act as master regulators of stem cell self-renewal and differentiation [1, 7]. These proteins function by binding to specific uridine-rich sequences in the 3' untranslated regions (UTRs) of target mRNAs, such as NUMB and CDKN1A, to modulate their translation and stability [3, 9]. While essential for normal development and the maintenance of neural and hematopoietic stem cell populations, Musashi proteins are frequently overexpressed in a wide range of malignancies, including acute myeloid leukemia (AML), glioblastoma, and colorectal cancer [1, 10]. In these contexts, they act as oncogenic drivers by promoting cell proliferation, inhibiting apoptosis, and maintaining the cancer stem cell phenotype [4, 16]. Due to their central role in tumor progression and therapy resistance, Musashi proteins have emerged as high-priority therapeutic targets [8, 11]. Current drug discovery efforts focus on small-molecule inhibitors and antisense oligonucleotides designed to disrupt the interaction between Musashi proteins and their cognate RNA targets, thereby suppressing oncogenic signaling and restoring normal cell fate [3, 12].

Other names

Musashi-1Musashi-2MSI1MSI2Nerve tissue protein Musashi-1Nerve tissue protein Musashi-2

Inhibition of RNA-binding activity by competitively binding to the RNA-recognition motifs (RRMs), thereby preventing the post-transcriptional regulation of target mRNAs involved in oncogenic signaling pathways.