XB-ART-56201Dev Dyn January 1, 2019; 248 (10): 969-978.
Overexpression of Lin28a delays Xenopus metamorphosis and down-regulates albumin independently of its translational regulation domain.
BACKGROUND: Lin28 regulates stem cell biology and developmental timing. At the molecular level Lin28 inhibits the biogenesis of the micro RNA let-7 and directly controls the transcription and translation of several genes. In Xenopus, Lin28 overexpression delays metamorphosis and affects the expression of genes of the thyroid hormone (TH) axis. The TH carrier albumin, synthesized by the liver, is down-regulated in limbs and tail after Lin28 overexpression. The molecular mechanisms underlying the interaction between Lin28, let-7, and the hypothalamus-pituitary-thyroid gland (HPT) axis are unknown. RESULTS: We found that precursor and mature forms of let-7 increase during Xenopus metamorphosis. In the liver, lin28b is down-regulated and albumin is up-regulated during metamorphosis. Overexpression of a truncated form of Lin28a (Lin28aΔC), which has been shown not to interact with RNA helicase A to regulate translation, delays metamorphosis, indicating that the translational regulation domain is not required to inhibit the HPT axis. Importantly, both full length Lin28a and Lin28aΔC block the increase of albumin mRNA in the liver independently of changes in TH signaling. CONCLUSIONS: These results suggest that Lin28 delays metamorphosis through regulation of let-7 and that the decrease of the TH carrier albumin is one of the early changes after Lin28 overexpression.
PubMed ID: 31397023
Article link: Dev Dyn
Species referenced: Xenopus laevis
Genes referenced: lin28a lin28b
GO keywords: metamorphosis
Article Images: [+] show captions
|Figure 3 Overexpression of Lin28ΔC. A, Protein sequences of Lin28a and Lin28aΔC‐flag highlighting the cold shock domain in green, the zinc‐knuckle domains in blue, the C‐terminal domain in brown and the flag epitope in red. B, Western blot with the anti‐flag epitope in tail samples of nontransgenic (−) and Lin28ΔC transgenic animals heat‐shocked for 3 weeks (three times per week). The specific band of Lin28ΔC‐flag is observed under 25 kDa. Nonspecific bands were detected above 75 kDa (asterisks) and were considered as loading control|