Dual regulation of miRNA biogenesis generates target specificity in neurotrophin-induced protein synthesis

Yu Wen A Huang, Claudia R. Ruiz, Elizabeth C H Eyler, Kathie Lin, Mollie K Meffert

Research output: Contribution to journalArticle

Abstract

Control of translation is a fundamental source of regulation in gene expression. The induction of protein synthesis by brain-derived neurotrophic factor (BDNF) critically contributes to enduring modifications of synaptic function, but how BDNF selectively affects only a minority of expressed mRNAs is poorly understood. We report that BDNF rapidly elevates Dicer, increasing mature miRNA levels and inducing RNA processing bodies in neurons. BDNF also rapidly induces Lin28, causing selective loss of Lin28-regulated miRNAs and a corresponding upregulation in translation of their target mRNAs. Binding sites for Lin28-regulated miRNAs are necessary and sufficient to confer BDNF responsiveness to a transcript. Lin28 deficiency, or expression of a Lin28-resistant Let-7 precursor miRNA, inhibits BDNF translation specificity and BDNF-dependent dendrite arborization. Our data establish that specificity in BDNF-regulated translation depends upon a two-part posttranscriptional control of miRNA biogenesis that generally enhances mRNA repression in association with GW182 while selectively derepressing and increasing translation of specific mRNAs.

Original languageEnglish (US)
Pages (from-to)933-946
Number of pages14
JournalCell
Volume148
Issue number5
DOIs
StatePublished - Mar 2 2012

Fingerprint

Brain-Derived Neurotrophic Factor
Nerve Growth Factors
MicroRNAs
Proteins
Messenger RNA
Neuronal Plasticity
Gene Expression Regulation
Protein Biosynthesis
Gene expression
Neurons
Up-Regulation
Binding Sites
Association reactions
RNA
Processing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Dual regulation of miRNA biogenesis generates target specificity in neurotrophin-induced protein synthesis. / Huang, Yu Wen A; Ruiz, Claudia R.; Eyler, Elizabeth C H; Lin, Kathie; Meffert, Mollie K.

In: Cell, Vol. 148, No. 5, 02.03.2012, p. 933-946.

Research output: Contribution to journalArticle

Huang, Yu Wen A ; Ruiz, Claudia R. ; Eyler, Elizabeth C H ; Lin, Kathie ; Meffert, Mollie K. / Dual regulation of miRNA biogenesis generates target specificity in neurotrophin-induced protein synthesis. In: Cell. 2012 ; Vol. 148, No. 5. pp. 933-946.
@article{219fdf1723d948c5b2723424babd3384,
title = "Dual regulation of miRNA biogenesis generates target specificity in neurotrophin-induced protein synthesis",
abstract = "Control of translation is a fundamental source of regulation in gene expression. The induction of protein synthesis by brain-derived neurotrophic factor (BDNF) critically contributes to enduring modifications of synaptic function, but how BDNF selectively affects only a minority of expressed mRNAs is poorly understood. We report that BDNF rapidly elevates Dicer, increasing mature miRNA levels and inducing RNA processing bodies in neurons. BDNF also rapidly induces Lin28, causing selective loss of Lin28-regulated miRNAs and a corresponding upregulation in translation of their target mRNAs. Binding sites for Lin28-regulated miRNAs are necessary and sufficient to confer BDNF responsiveness to a transcript. Lin28 deficiency, or expression of a Lin28-resistant Let-7 precursor miRNA, inhibits BDNF translation specificity and BDNF-dependent dendrite arborization. Our data establish that specificity in BDNF-regulated translation depends upon a two-part posttranscriptional control of miRNA biogenesis that generally enhances mRNA repression in association with GW182 while selectively derepressing and increasing translation of specific mRNAs.",
author = "Huang, {Yu Wen A} and Ruiz, {Claudia R.} and Eyler, {Elizabeth C H} and Kathie Lin and Meffert, {Mollie K}",
year = "2012",
month = "3",
day = "2",
doi = "10.1016/j.cell.2012.01.036",
language = "English (US)",
volume = "148",
pages = "933--946",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - Dual regulation of miRNA biogenesis generates target specificity in neurotrophin-induced protein synthesis

AU - Huang, Yu Wen A

AU - Ruiz, Claudia R.

AU - Eyler, Elizabeth C H

AU - Lin, Kathie

AU - Meffert, Mollie K

PY - 2012/3/2

Y1 - 2012/3/2

N2 - Control of translation is a fundamental source of regulation in gene expression. The induction of protein synthesis by brain-derived neurotrophic factor (BDNF) critically contributes to enduring modifications of synaptic function, but how BDNF selectively affects only a minority of expressed mRNAs is poorly understood. We report that BDNF rapidly elevates Dicer, increasing mature miRNA levels and inducing RNA processing bodies in neurons. BDNF also rapidly induces Lin28, causing selective loss of Lin28-regulated miRNAs and a corresponding upregulation in translation of their target mRNAs. Binding sites for Lin28-regulated miRNAs are necessary and sufficient to confer BDNF responsiveness to a transcript. Lin28 deficiency, or expression of a Lin28-resistant Let-7 precursor miRNA, inhibits BDNF translation specificity and BDNF-dependent dendrite arborization. Our data establish that specificity in BDNF-regulated translation depends upon a two-part posttranscriptional control of miRNA biogenesis that generally enhances mRNA repression in association with GW182 while selectively derepressing and increasing translation of specific mRNAs.

AB - Control of translation is a fundamental source of regulation in gene expression. The induction of protein synthesis by brain-derived neurotrophic factor (BDNF) critically contributes to enduring modifications of synaptic function, but how BDNF selectively affects only a minority of expressed mRNAs is poorly understood. We report that BDNF rapidly elevates Dicer, increasing mature miRNA levels and inducing RNA processing bodies in neurons. BDNF also rapidly induces Lin28, causing selective loss of Lin28-regulated miRNAs and a corresponding upregulation in translation of their target mRNAs. Binding sites for Lin28-regulated miRNAs are necessary and sufficient to confer BDNF responsiveness to a transcript. Lin28 deficiency, or expression of a Lin28-resistant Let-7 precursor miRNA, inhibits BDNF translation specificity and BDNF-dependent dendrite arborization. Our data establish that specificity in BDNF-regulated translation depends upon a two-part posttranscriptional control of miRNA biogenesis that generally enhances mRNA repression in association with GW182 while selectively derepressing and increasing translation of specific mRNAs.

UR - http://www.scopus.com/inward/record.url?scp=84863230304&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863230304&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2012.01.036

DO - 10.1016/j.cell.2012.01.036

M3 - Article

VL - 148

SP - 933

EP - 946

JO - Cell

JF - Cell

SN - 0092-8674

IS - 5

ER -