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Messenger RNAs and cognate microRNAs in the nucleolus (940.3)

During studies of muscle cell differentiation in a rat myogenic cell line we discovered, to our surprise, that several microRNAs are concentrated in the nucleolus (Politz et al., PNAS 103: 18957‐18962, 2006; RNA 15:1705‐1715, 2009). Since these nucleolus‐localized microRNAs were also present in the cytoplasm, it seemed plausible that their association with nucleoli represented a station on their nuclear export pathway. These findings prompted us to ask whether certain messenger RNAs might also localized in the nucleoli of these cells. Microarray analysis of RNA from highly purified nucleoli revealed a set of mRNAs present at 30 to 650‐fold higher concentrations than in the nucleoplasm and this was confirmed by in situ hybridization for one of these mRNAs, that encoding insulin‐like growth factor 2 (IGF2), an well‐known autocrine regulator of myoblast proliferation and differentiation. RT‐PCR experiments demonstrated that these nucleolus‐localized IGF2 transcripts are spliced mRNAs, suggesting that they arrive from distal sites in the nucleoplasm. Bioinformatics analysis predicted stable interactions between all of the nucleolus‐localized microRNAs and the 5′ or 3′ untranslated regions of IGF2 mRNA. Additional considerations suggest that at least one of the nucleolus‐localized microRNAs, miR‐206, may be involved in the positive regulation of IGF2 mRNA translation and we speculate that transit through the nucleolus commits IGF2 mRNA to this mode of regulation.