Overexpression of Lin28a delays Xenopus metamorphosis and down‐regulates albumin independently of its translational regulation domain

Abstract

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.

A Novel Perspective on Neuronal Control of Anatomical Patterning, Remodeling, and Maintenance

“…For example, studies have shown that humans utilize thyroid hormones T3 and T4, important endocrine modulators in amphibian metamorphosis, during the pre to postnatal transition period [173][174][175]. Additionally, studies have found that a genetic loci involved in the metamorphic timing of C. elegans and Xenopus laevis is conserved in humans for the modulation of sexual maturation [176][177][178]. Evidence of these shared mechanisms suggests a closer tie between metamorphosis and human growth and maturation than previously considered, and it may be an important route of exploration in the future.…”