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A Rapid Induction Mechanism for Lin28a in Trophic Responses.

Molecular cell | 2017

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.

Pubmed ID: 28132840 RIS Download

Associated grants

  • Agency: NINDS NIH HHS, United States
    Id: P30 NS050274
  • Agency: NIMH NIH HHS, United States
    Id: P50 MH084020
  • Agency: NIMH NIH HHS, United States
    Id: F31 MH098634
  • Agency: NIMH NIH HHS, United States
    Id: F31 MH103902
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH109341
  • Agency: NIMH NIH HHS, United States
    Id: R01 MH098016

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This is a list of tools and resources that we have found mentioned in this publication.


New England Biolabs (tool)

RRID:SCR_013517

An Antibody supplier

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Anti-LIN28A / LIN28 Antibody (antibody)

RRID:AB_2714144

This polyclonal targets LIN28A / LIN28

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normal rabbit IgG (antibody)

RRID:AB_737197

This unknown targets normal rabbit IgG

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mouse-IgG-control-human (antibody)

RRID:AB_737182

This unknown targets mouse-IgG-control

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β-Actin Antibody (antibody)

RRID:AB_330288

This polyclonal targets β-actin

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NF2 / Merlin antibody [AF1G4] (antibody)

RRID:AB_2042307

This monoclonal targets NF2 / Merlin antibody [AF1G4]

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HSC 70 (B-6) (antibody)

RRID:AB_627761

This monoclonal targets HSC 70 (B-6)

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LIN28B Antibody (Mouse Preferred) (antibody)

RRID:AB_10697489

This polyclonal targets LIN28B (Mouse Preferred)

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Dicer (H-212) (antibody)

RRID:AB_639122

This polyclonal targets Dicer (H-212)

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DICER1-human (antibody)

RRID:AB_10603336

This polyclonal targets DICER1

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TRBP antibody (antibody)

RRID:AB_2200485

This polyclonal targets TRBP

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TRBP antibody (antibody)

RRID:AB_1271291

This polyclonal targets TRBP antibody

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Lin28 Antibody (antibody)

RRID:AB_10011591

This polyclonal targets Lin28

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LIN28A (A177) Antibody (antibody)

RRID:AB_2297060

This polyclonal targets LIN28

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HEK293T/17 (cell line)

RRID:CVCL_1926

Cell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)

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GeneTraffic (software resource)

RRID:SCR_008651

GeneTraffic is a web-based microarray data analysis and management software developed by Iobion Informatics that allows users to log onto a server, upload their microarray data and perform analysis and project management remotely. GeneTraffic was made by Iobion Informatics (now under Stratagene) and can be accessed thorough Internet Explorer 6.0 or greater on Windows XP.

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Imaris (software resource)

RRID:SCR_007370

Imaris provides range of capabilities for working with three dimensional images. Uses flexible editing and processing functions, such as interactive surface rendering and object slicing capabilities. And output to standard TIFF, Quicktime and AVI formats. Imaris accepts virtually all image formats that are used in confocal microscopy and many of those used in wide-field image acquisition.

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HEK293T/17 (cell line)

RRID:CVCL_1926

Cell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions

HEK293T/17 (cell line)

RRID:CVCL_1926

Cell line HEK293T/17 is a Transformed cell line with a species of origin Homo sapiens (Human)

View all literature mentions