| First Author | Amen AM | Year | 2017 |
| Journal | Mol Cell | Volume | 65 |
| Issue | 3 | Pages | 490-503.e7 |
| PubMed ID | 28132840 | Mgi Jnum | J:252864 |
| Mgi Id | MGI:6094301 | Doi | 10.1016/j.molcel.2016.12.025 |
| Citation | Amen AM, et al. (2017) A Rapid Induction Mechanism for Lin28a in Trophic Responses. Mol Cell 65(3):490-503.e7 |
| abstractText | Environmental cues provoke rapid transitions in gene expression to support growth and cellular plasticity through incompletely understood mechanisms. Lin28 RNA-binding proteins have evolutionarily conserved roles in post-transcriptional coordination of pro-growth gene expression, but signaling pathways allowing trophic stimuli to induce Lin28 have remained uncharacterized. We find that Lin28a protein exhibits rapid basal turnover in neurons and that mitogen-activated protein kinase (MAPK)-dependent phosphorylation of the RNA-silencing factor HIV TAR-RNA-binding protein (TRBP) promotes binding and stabilization of Lin28a, but not Lin28b, with an accompanying reduction in Lin28-regulated miRNAs, downstream of brain-derived neurotrophic factor (BDNF). Binding of Lin28a to TRBP in vitro is also enhanced by phospho-mimic TRBP. Further, phospho-TRBP recapitulates BDNF-induced neuronal dendritic spine growth in a Lin28a-dependent manner. Finally, we demonstrate MAPK-dependent TRBP and Lin28a induction, with physiological function in growth and survival, downstream of diverse growth factors in multiple primary cell types, supporting a broad role for this pathway in trophic responses. |
