A mirror of two faces: Lin28 as a master regulator of both miRNA and mRNA.

Lin28 is an evolutionarily conserved RNA-binding protein that plays important roles in development, pluripotency, tumorigenesis, and metabolism. Emerging evidence suggests that the pleiotropic roles of Lin28 in the diverse physiological and pathological processes are mechanistically linked to its ability to modulate not only the biogenesis of miRNAs, particularly the let-7 family miRNAs, but also the translation of mRNAs important for cell growth and metabolism. Let-7 negatively regulates the translation of oncogenes, cell cycle regulators, and metabolic pathway components. Lin28 relieves this repression by blocking the production of mature let-7. Lin28 binds to the terminal loops of let-7 precursors, leading to inhibition of processing and the induction of uridylation and precursor degradation. Lin28 also is a direct translational regulator: it selectively binds to a cohort of mRNAs and stimulates their translation. Recent advances in our understanding of Lin28-mediated mechanisms of posttranscriptional regulation of gene expression reveal important roles of this protein in the fields of development, stem cells, metabolic diseases, and cancer.