SUN-088 - The Musashi Messenger Ribonucleoprotein Complex in Translational Regulation of Pituitary Mrnas

The pituitary is a master endocrine gland that coordinates systemic hormonal activity. The pituitary exhibits a high degree of plasticity and is able to remodel its hormone-producing cell population in response to changing organismal demands. Our recent work has implicated Musashi (MSI), a sequence-specific RNA binding protein, as a mediator of pituitary plasticity. MSI modulates stem cell function and plasticity across a variety of tissues via mRNA translational regulation and is highly expressed in both mature hormone-producing cells and stem cells of the anterior pituitary (AP). MSI is bifunctional, able to activate or repress target mRNA translation in a context-dependent manner. In the AP, MSI represses Pou1f1/Pit1, Gnrhr, Fshb, Prl, and Tshb and activates Prop1, Gata2, and Nr5a1 (SF-1). The mechanisms that determine whether MSI acts as an activator or repressor of mRNA translation are not currently known. We hypothesize that MSI facilitates hormone-producing AP cell plasticity through selective activation or repression via recruitment of MSI co-associated proteins and formation of distinct messenger ribonucleoprotein (mRNP) regulatory complexes. To test this, we will isolate activation- or repression-associated MSI mRNP complexes by S1-aptamer pulldown of “mini RNAs” (composed of a 5’ UTR, a short open reading frame (sORF), a modified streptavidin-binding RNA aptamer (S1 aptamer) tag downstream of the stop codon, and a 3’ UTR associated with MSI-dependent repression (Gnrhr, Fshb) or activation (Prop1, Gata2)). Activation- and repression-associated proteins will be identified by quantitative mass spectrometry following S1 aptamer pulldown. We have confirmed that MSI1 binds to RNA containing an S1-tagged mouse Prop1 3’ UTR and is successfully isolated by S1 aptamer pulldown. Ongoing studies employ mass spectrometry to identify activation- or repression-specific MSI co-associated proteins. Future studies will assess the functional role of proteins in activation- or repression-associated MSI mRNP complexes in LBT2 (mouse gonadotrope) cells and mouse whole pituitaries.

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