MSi2

MSi2, also known as MSI2 or Musashi-2, is an RNA-binding protein in animals that plays a role in post-transcriptional gene regulation. It is a member of the Musashi family, which includes MSI1, and is encoded by the MSI2 gene.

MSI2 contains two RNA recognition motifs (RRMs) that allow it to bind to U-rich sequences in the 3' untranslated regions of target mRNAs and regulate their translation. In many contexts, MSI2 represses translation of target mRNAs such as NUMB, thereby influencing Notch signaling and cell fate decisions. Depending on context, it can also affect other targets and pathways.

In vertebrates, MSI2 is important for the maintenance and expansion of hematopoietic stem and progenitor cells; it is also expressed in neural and other developing tissues. In mice, MSI2 activity supports self-renewal and proper progenitor function; loss or reduction can impair hematopoiesis.

MSI2 overexpression has been observed in several cancers, including subsets of acute myeloid leukemia and some solid tumors, and is associated with poorer prognosis in some patient cohorts. Because of its role in sustaining stem-like properties, MSI2 is studied as a potential therapeutic target.

Strategies under investigation aim to disrupt MSI2’s RNA-binding activity or downstream signaling, but no MSI2-targeted therapies are currently approved.