Phospho-LIN28A (Ser200)

Full Name

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).

Biological Process

Cellular response to glucose stimulusISS:BHF-UCL
Germ cell developmentIEA:Ensembl
miRNA catabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of glial cell differentiationIEA:Ensembl
Negative regulation of translationISS:UniProtKB
Positive regulation of cell proliferation involved in kidney developmentIEA:Ensembl
Positive regulation of cytoplasmic translationManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of neuron differentiationIEA:Ensembl
Positive regulation of production of miRNAs involved in gene silencing by miRNAISS:BHF-UCL
Positive regulation of protein kinase B signalingISS:BHF-UCL
Positive regulation of TOR signalingISS:BHF-UCL
Pre-miRNA processingManual Assertion Based On ExperimentIMP:UniProtKB
RNA 3' uridylationIEA:Ensembl
RNA 3'-end processingManual Assertion Based On ExperimentIMP:UniProtKB
Stem cell differentiationIEA:Ensembl
Stem cell population maintenanceManual Assertion Based On ExperimentIMP:UniProtKB

Cellular Location

Cytoplasm
Rough endoplasmic reticulum
Cytoplasm, P-body
Cytoplasm, Stress granule
Nucleus, nucleolus
Predominantly cytoplasmic (PubMed:22118463).
In the cytoplasm, localizes to peri-endoplasmic reticulum regions and detected in the microsomal fraction derived from rough endoplasmic reticulum (RER) following subcellular fractionation. May be bound to the cytosolic surface of RER on which ER-associated mRNAs are translated (By similarity).
Shuttle from the nucleus to the cytoplasm requires RNA-binding (PubMed:17617744).
Nucleolar localization is observed in 10-15% of the nuclei in differentiated myotubes (By similarity).