LIN28-TAT Human Active Protein

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. Ref.12 Ref.13

Subunit structure: 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. Ref.13

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. Ref.11 Ref.12

Tissue specificity: Expressed in embryonic stem cells (ES cells), placenta and testis. Ref.7 Ref.8 Ref.9

Developmental stage: Expressed in fetal liver. Expression decreases during differentiation of ES cells or upon induction of neuronal differentiation by retinoic acid. Ref.7 Ref.8 Ref.9

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. Ref.6 Ref.10

Domain: The CSD domain is required for function in muscle differentiation

By similarity.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.

Sequence similarities: Belongs to the lin-28 family.Contains 2 CCHC-type zinc fingers.Contains 1 CSD (cold-shock) domain.