LIN28

Lin-28 homolog A is a is_associated_with::protein that in humans is encoded by the LIN28 is_associated_with::gene.

LIN28 encodes a is_associated_with::microRNA-binding protein that binds to and enhances the translation of the IGF-2 (insulin-like growth factor 2) mRNA. Lin28 binds to the let-7 pre-is_associated_with::microRNA and blocks production of the mature let-7 microRNA in mouse is_associated_with::embryonic stem cells. In is_associated_with::pluripotent embryonal is_associated_with::carcinoma cells, LIN28 is localized in the is_associated_with::ribosomes, P-bodies and is_associated_with::stress granules.

Stem cell expression
LIN28 is thought to regulate the self-renewal of is_associated_with::stem cells. In is_associated_with::nematodes, the LIN28 is_associated_with::homolog lin-28 is a heterochronic gene that determines the onset of early larval stages of developmental events in is_associated_with::Caenorhabditis elegans, by regulating the self-renewal of nematode stem cells in the skin (called seam cells) and is_associated_with::vulva (called VPCs) during development. In mice, LIN28 is highly expressed in mouse embryonic stem cells and during early is_associated_with::embryogenesis.

LIN28 is highly expressed in human embryonic stem cells and can enhance the efficiency of the formation of induced pluripotent stem (iPS) cells from human is_associated_with::fibroblasts.

Puberty
LIN28 overexpression in mice can cause is_associated_with::gigantism and a delay in is_associated_with::puberty onset, consistent with human genome-wide association studies suggesting that polymorphisms in the human LIN28B gene are associated with human height and is_associated_with::puberty timing. Mutations in LIN28B are associated with is_associated_with::precocious puberty.

LIN28 can regulate glucose homeostasis in mammals by increasing is_associated_with::insulin-is_associated_with::PI3K-is_associated_with::mTOR signaling and insulin sensitivity, thereby promoting resistance to high fat diet-induced is_associated_with::obesity and type 2 is_associated_with::diabetes.

Tissue regeneration
Mice genetically altered to produce LIN28 during their lifespan showed improved is_associated_with::hair growth. and healthy tissue regeneration on added puncture wounds in later life stages. While the mice could regenerate limbs, they could not repair damaged heart tissue. Appropriate drugs replicated the regeneration in unaltered mice, using the same metabolic paths. The drugs increased the subjects' metabolic rates, evidently causing the body to heal at higher rates. The effects of Lin28a activation faded with age.

Structure
Crystallographic structures of Lin28/let-7 complexes reveal that two folded domains of Lin28 recognize two distinct is_associated_with::RNA regions. The domains are sufficient for inhibition of let-7 is_associated_with::in vivo.

Applications
LIN28 is a marker of undifferentiated human embryonic is_associated_with::stem cells and has been used to enhance the efficiency of the formation of iPS cells from human is_associated_with::fibroblasts.