Abstract：
: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.
journal_name
Mol Celljournal_title
Molecular cellauthors
Amen AM,Ruiz-Garzon CR,Shi J,Subramanian M,Pham DL,Meffert MKdoi
10.1016/j.molcel.2016.12.025subject
Has Abstractpub_date
2017-02-02 00:00:00pages
490-503.e7issue
3eissn
1097-2765issn
1097-4164pii
S1097-2765(16)30868-1journal_volume
65pub_type
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