The hetero chonicgene Lin28 is a regulator of developmental timing of larval and vulval development in Caenorhabditis elegans but have recently been implicated in cancer, stem cell aging and pluropotency. Proto-oncogene, Lin28 is an RNA binding protein expressed in most of the developing tissues. There are 2 isoforms of Lin28, Lin28B and its homolog Lin28A are functionally redundant RNA-binding proteins that block biogenesis of let-7 microRNAs in embryonic stem cells and in certain cancer cell lines (1). The pluropotency-promoting protein Lin28A and Lin28B act as post-transcriptional repressors of Let-7 miRNA biogenesis in undifferentiated mouse embryonic cells. The precursor of Let7 (pre-Let-7) is terminally urdylated in a Lin28-dependent fashion via Zcchc11 as 3’-terminal uridylyl transferase (TUTase) which causes a blockade of Let7 processing in mouse embryonic cells (2). The levels of mature let-7a differs significantly in cells lacking Lin28 expression suggesting additional mechanisms for post-transcriptional regulation. One of such regulatory mechanism was via heteronuclear ribonucleoprotein A1 (hnRNP A1) acting as a repressor of Let7 (3). The Lin28-mediated down-regulation of let-7 may play a key role in development, stem cell programming, and tumorigenesis.
Lin28A is a 209 amino acid (25kDa) soluble protein expressed in stem cells and in majority of developing cells.
The protein has several functional domains in the RNA binding site that has a S1-like domain similar to cold shock
domain generally found in eukaryotes and archaea. These proteins are expressed when there is sudden drop in
growth temperature. Other domains include RNA chaperone, CSPC, D, E etc. Near C-temrinal end there is arginine
methyl transferase interacting protein mainly involved in intracellular trafficking and secretion.
For research use only, not for diagnostic or therapeutic use.
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