AI Article Synopsis
- Genome-wide studies suggest that the LIN28B gene is linked to height and the onset of menarche in humans.
- LIN28B and LIN28A are RNA-binding proteins that inhibit the production of let-7 microRNAs, which play roles in development and have implications for cancer and stem cell biology.
- Transgenic mice expressing Lin28a showed enhanced body size and delayed puberty, along with changes in metabolism, providing a model for understanding the effects of the Lin28-Let-7 pathway on human traits.
Article Abstract
Recently, genome-wide association studies have implicated the human LIN28B locus in regulating height and the timing of menarche. LIN28B and its homolog LIN28A are functionally redundant RNA-binding proteins that block biogenesis of let-7 microRNAs. lin-28 and let-7 were discovered in Caenorhabditis elegans as heterochronic regulators of larval and vulval development but have recently been implicated in cancer, stem cell aging and pluripotency. The let-7 targets Myc, Kras, Igf2bp1 and Hmga2 are known regulators of mammalian body size and metabolism. To explore the function of the Lin28-Let-7 pathway in vivo, we engineered transgenic mice to express Lin28a and observed in them increased body size, crown-rump length and delayed onset of puberty. Investigation of metabolic and endocrine mechanisms of overgrowth in these transgenic mice revealed increased glucose metabolism and insulin sensitivity. Here we report a mouse that models the human phenotypes associated with genetic variation in the Lin28-Let-7 pathway.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069638 | PMC |
| http://dx.doi.org/10.1038/ng.593 | DOI Listing |
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