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spinqualitylabelsall models pdb 2cqf protein lin28A Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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Lin28 is a conserved cytoplasmic protein with an unusual pairing of RNA‑binding motifs: a cold shock domain and a pair of retroviral‑type CCHC zinc fingers.

Lin28 is a conserved cytoplasmic protein with an unusual pairing of RNA binding motifs: a cold shock domain and a pair of retroviral type CCHC zinc fingers. It plays a critical role in developmental transition, glucose metabolism, and tumorigenesis. At the molecular level, Lin28 is known to repress maturation of let-7 microRNAs and enhance translation of certain mRNAs. Mammals have two homologs, Lin28a and Lin28b. These two homologs are found from worms to humans ; Balzer and Moss, 2007). Lin28a is highly expressed in embryonic stem cells (ESCs) and was shown as one of the four factors that convert fibroblasts into induced pluripotent stem cells (Yu et al., 2007).

At the molecular level, Lin28 acts as a suppressor of let-7 microRNA biogenesis (Heo et al., 2008; Newman et al., 2008; Rybak et al., 2008; Viswanathan et al., 2008). In the nucleus, Lin28 binds to the primary transcript of let-7 (pri-let-7) and prevents its processing by RNase III DROSHA (Newman et al., 2008; Viswanathan et al., 2008). In the cytoplasm, it interacts with the precursor form of let-7 (pre-let-7) and interferes with pre-let-7 processing (Heo et al., 2008; Rybak et al., 2008). Lin28 recruits TUTase 4 (ZCCHC11) to induce oligo-uridylation of pre-let-7, which effectively blocks DICER processing and facilitates degradation of the RNA (Hagan et al., 2009; Heo et al., 2008; Heo et al., 2009). Lin28A is found mostly in the cytoplasmic compartment and acts in concert with TUTase 4 (Piskounova et al., 2011).

Let-7 is a key target of Lin28 but there are four additional functions: First, during retinoic-acid-induced neurogliogenesis, Lin28a overexpression altered the expression of several transcription factors involved in early embryonic cell fate decision before any increase in let-7 level was detected (Balzer et al., 2010). Second, impaired glucose tolerance and insulin resistance were observed in muscle-specific Lin28a knockout mice without significant changes in the let-7 level (Zhu et al., 2011). Third, Lin28A interacts with mRNAs and cosediments with polysome in sucrose gradient centrifugation (Balzer and Moss, 2007). Consistently, several studies reported that Lin28A can bind to and enhance translation of certain mRNAs such as Igf2 in differentiating myoblasts and Oct4 in ESCs (Polesskaya et al., 2007; Qiu et al., 2010; Xu and Huang, 2009; Xu et al., 2009).

ContributorsContributors

Katrin Frohnmüller, Teresa Wiese

spinqualitylabelsall models pdb 2li8 crystall structure lin28A/let-7 Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image