LIN28A

Developmental stage

Expressed in fetal liver. Expression decreases during differentiation of ES cells or upon induction of neuronal differentiation by retinoic acid.

Domain

The CSD domain is required for function in muscle differentiation.

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.

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. This results in the terminal uridylation of target pre-miRNAs. 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).

Sequence similarities

Belongs to the lin-28 family.

Tissue specificity

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

Cellular localization

• 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).

Alternative names

• Protein lin-28 homolog A
• Lin-28A
• Zinc finger CCHC domain-containing protein 1
• LIN28A
• CSDD1
• LIN28
• ZCCHC1

Database links

• entrezGene:79727
• omim:611043
• swissprot:Q9H9Z2

Target type

Proteins

Molecular weight

22743Da