Recombinant Human Protein lin-28 homolog A (LIN28A), partial

Function

RNA-binding protein that inhibits processing of pre-let-7 miRNAs and regulates translation of mRNAs that control developmental timing, pluripotency and metabolism (PubMed:21247876). Seems to recognize a common structural G-quartet (G4) feature in its miRNA and mRNA targets (Probable). 'Translational enhancer' that drives specific mRNAs to polysomes and increases the efficiency of protein synthesis. Its association with the translational machinery and target mRNAs results in an increased number of initiation events per molecule of mRNA and, indirectly, in mRNA stabilization. Binds IGF2 mRNA, MYOD1 mRNA, ARBP/36B4 ribosomal protein mRNA and its own mRNA. Essential for skeletal muscle differentiation program through the translational up-regulation of IGF2 expression. Suppressor of microRNA (miRNA) biogenesis, including that of let-7, miR107, miR-143 and miR-200c. Specifically binds the miRNA precursors (pre-miRNAs), recognizing an 5'-GGAG-3' motif found in pre-miRNA terminal loop, and recruits TUT4 and TUT7 uridylyltransferases (PubMed:18951094, PubMed:19703396, PubMed:22118463, PubMed:22898984). This results in the terminal uridylation of target pre-miRNAs (PubMed:18951094, PubMed:19703396, PubMed:22118463, PubMed:22898984). Uridylated pre-miRNAs fail to be processed by Dicer and undergo degradation. The repression of let-7 expression is required for normal development and contributes to maintain the pluripotent state by preventing let-7-mediated differentiation of embryonic stem cells (PubMed:18951094, PubMed:19703396, PubMed:22118463, PubMed:22898984). Localized to the periendoplasmic reticulum area, binds to a large number of spliced mRNAs and inhibits the translation of mRNAs destined for the ER, reducing the synthesis of transmembrane proteins, ER or Golgi lumen proteins, and secretory proteins. Binds to and enhances the translation of mRNAs for several metabolic enzymes, such as PFKP, PDHA1 or SDHA, increasing glycolysis and oxidative phosphorylation. Which, with the let-7 repression may enhance tissue repair in adult tissue (By similarity)

Subcellular Location

Cytoplasm; Rough endoplasmic reticulum; Cytoplasm, P-body; Cytoplasm, Stress granule; Nucleus, nucleolus

Tissue Specificity

Expressed in embryonic stem cells, placenta and testis. Tends to be up-regulated in HER2-overexpressing breast tumors

Subunit

Monomer (By similarity). During skeletal muscle differentiation, associated with translation initiation complexes in the polysomal compartment (PubMed:21247876). Directly interacts with EIF3S2 (By similarity). Interacts with NCL in an RNA-dependent manner (By similarity). Interacts (via C-terminus) with DHX9 (via N- and C-terminus); this interaction occurs in a RNA-independent manner (PubMed:21247876). Interacts with TUT4 in the presence of pre-let-7 RNA (PubMed:19703396, PubMed:22118463)

• Moss E.G. et al. Conservation of the heterochronic regulator Lin-28, its developmental expression and microRNA complementary sites. — Dev. Biol. (2003)
• Moss E.G. et al. PubMed: CI-3M2M76EGOVI9M — Dev. Biol. (2003)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Gregory S.G. et al. The DNA sequence and biological annotation of human chromosome 1. — Nature (2006)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Sempere L.F. et al. Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. — Genome Biol. (2004)
• Richards M. et al. The transcriptome profile of human embryonic stem cells as defined by SAGE. — Stem Cells (2004)
• Gerecht-Nir S. et al. Vascular gene expression and phenotypic correlation during differentiation of human embryonic stem cells. — Dev. Dyn. (2005)