Human Gene LIN28A (ENST00000326279.11) from GENCODE V44
Description: Homo sapiens lin-28 homolog A (LIN28A), mRNA. (from RefSeq NM_024674) RefSeq Summary (NM_024674): This gene encodes a LIN-28 family RNA-binding protein that acts as a posttranscriptional regulator of genes involved in developmental timing and self-renewal in embryonic stem cells. The encoded protein functions through direct interaction with target mRNAs and by disrupting the maturation of certain miRNAs involved in embryonic development. This protein prevents the terminal processing of the LET7 family of microRNAs which are major regulators of cellular growth and differentiation. Aberrant expression of this gene is associated with cancer progression in multiple tissues. [provided by RefSeq, Sep 2015]. Sequence Note: This RefSeq record was created from transcript and genomic sequence data to make the sequence consistent with the reference genome assembly. The genomic coordinates used for the transcript record were based on transcript alignments. Gencode Transcript: ENST00000326279.11 Gencode Gene: ENSG00000131914.11 Transcript (Including UTRs) Position: hg38 chr1:26,410,817-26,429,728 Size: 18,912 Total Exon Count: 4 Strand: + Coding Region Position: hg38 chr1:26,410,892-26,426,458 Size: 15,567 Coding Exon Count: 4
ID:LN28A_HUMAN DESCRIPTION: RecName: Full=Protein lin-28 homolog A; Short=Lin-28A; AltName: Full=Zinc finger CCHC domain-containing protein 1; FUNCTION: Acts as a 'translational enhancer', driving specific mRNAs to polysomes and thus increasing 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 stabilizing the mRNAs. 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 (By similarity). Acts as a suppressor of microRNA (miRNA) biogenesis by specifically binding the precursor let-7 (pre-let- 7), a miRNA precursor. Acts by binding pre-let-7 and recruiting ZCCHC11/TUT4 uridylyltransferase, leading to the terminal uridylation of pre-let-7. Uridylated pre-let-7 miRNAs fail to be processed by Dicer and undergo degradation. Degradation of pre- let-7 in embryonic stem (ES) cells contributes to the maintenance of ES cells. In contrast, LIN28A down-regulation in neural stem cells by miR-125, allows the processing of pre-let-7. Specifically recognizes the 5'-GGAG-3' motif in the terminal loop of pre-let-7. Also recognizes and binds non pre-let-7 pre-miRNAs that contain the 5'-GGAG-3' motif in the terminal loop, leading to their terminal uridylation and subsequent degradation. SUBUNIT: Monomer. During skeletal muscle differentiation, associated with translation initiation complexes in the polysomal compartment. Directly interacts with EIF3S2. Interaction with NCL is RNA-dependent (By similarity). Interacts with ZCCHC11/TUT4. SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleolus. Note=Nucleolar localization observed in 10-15% of the nuclei in differentiated myotubes (By similarity). Shuttles between the cytoplasm and the nucleus. Localizes to cytoplasmic processing bodies and stress granules. TISSUE SPECIFICITY: Expressed in embryonic stem cells (ES cells), placenta and testis. DEVELOPMENTAL STAGE: Expressed in fetal liver. Expression decreases during differentiation of ES cells or upon induction of neuronal differentiation by retinoic acid. INDUCTION: Can be negatively regulated by the interaction of microRNAs miR-125a and miR-125b with at least two miRNA responsive elements (miREs) in the 3'-UTR of this gene. These interactions may reduce both translation efficiency and mRNA abundance. Negatively regulated by retinoic acid. DOMAIN: The CSD domain is required for function in muscle differentiation (By similarity). DOMAIN: The CCHC zinc fingers interact with the GGAG motif at the 3' end of let-7 miRNAs precursors, more generally they bind the 5'-NGNNG-3' consensus motif with micromolar affinity. The CSD domain recognizes the loop at the 5' end. The flexible linker allows accommodating variable sequences and lengths among let-7 family members. MISCELLANEOUS: Overexpressed in primary tumors (overall frequency approximately 15%), overexpression being linked to repression of let-7 family miRNAs and derepression of let-7 targets. Facilitates cellular transformation in vitro, and overexpression is associated with advanced disease across multiple tumor types. SIMILARITY: Belongs to the lin-28 family. SIMILARITY: Contains 2 CCHC-type zinc fingers. SIMILARITY: Contains 1 CSD (cold-shock) domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q9H9Z2
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006355 regulation of transcription, DNA-templated GO:0007281 germ cell development GO:0010586 miRNA metabolic process GO:0010587 miRNA catabolic process GO:0017148 negative regulation of translation GO:0019827 stem cell population maintenance GO:0031047 gene silencing by RNA GO:0031054 pre-miRNA processing GO:0031123 RNA 3'-end processing GO:0032008 positive regulation of TOR signaling GO:0035019 somatic stem cell population maintenance GO:0045666 positive regulation of neuron differentiation GO:0045686 negative regulation of glial cell differentiation GO:0045727 positive regulation of translation GO:0048863 stem cell differentiation GO:0051897 positive regulation of protein kinase B signaling GO:0060964 regulation of gene silencing by miRNA GO:0071333 cellular response to glucose stimulus GO:1901724 positive regulation of cell proliferation involved in kidney development GO:1903800 positive regulation of production of miRNAs involved in gene silencing by miRNA GO:2000767 positive regulation of cytoplasmic translation
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