In neurons, activity-dependent association of dendritically transported mRNA transcripts with the transacting factor CBF-A is mediated by A2RE/RTS elements

Chandrasekhar S. Raju, Nanaho Fukuda, Carmen López-Iglesias, Christian Göritz, Neus Visa, Piergiorgio Percipalle

Research output: Contribution to journalArticle

Abstract

In neurons certain mRNA transcripts are transported to synapses through mechanisms that are not fully understood. Here we report that the heterogeneous nuclear ribonucleoprotein CBF-A (CArG Box binding Factor A) facilitates dendritic transport and localization of activity-regulated cytoskeleton- associated protein (Arc), brain-derived neurotrophic factor (BDNF), and calmodulin-dependent protein kinase II (CaMKIIα) mRNAs. We discovered that, in the adult mouse brain, CBF-A has a broad distribution. In the nucleus, CBF-A was found at active transcription sites and interchromosomal spaces and close to nuclear pores. In the cytoplasm, CBF-A localized to dendrites as well as pre- and postsynaptic sites. CBF-A was found in synaptosomal fractions, associated with Arc, BDNF, and CaMKIIα mRNAs. Electrophoretic mobility shift assays demonstrated a direct interaction mediated via their hnRNP A2 response element (A2RE)/RNA trafficking sequence (RTS) elements located in the 3′ untranslated regions. In situ hybridization and microscopy on live hippocampal neurons showed that CBF-A is in dynamic granules containing Arc, BDNF, and CaMKIIα mRNAs. N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) postsynaptic receptor stimulation led to CBF-A accumulation in dendrites; increased Arc, BDNF, and CaMKIIα mRNA levels; and increased amounts of transcripts coprecipitating with CBF-A. Finally, CBF-A gene knockdown led to decreased mRNA levels. We propose that CBF-A cotranscriptionally binds RTSs in Arc, BDNF, and CaMKIIα mRNAs and follows the transcripts from genes to dendrites, promoting activity-dependent nuclear sorting of transport-competent mRNAs.

Original languageEnglish (US)
Pages (from-to)1864-1877
Number of pages14
JournalMolecular Biology of the Cell
Volume22
Issue number11
DOIs
StatePublished - Jun 1 2011

Fingerprint

Response Elements
varespladib methyl
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Brain-Derived Neurotrophic Factor
Neurons
Messenger RNA
Dendrites
Heterogeneous-Nuclear Ribonucleoproteins
Gene Knockdown Techniques
Isoxazoles
Nuclear Pore
AMPA Receptors
Cell Nucleus Active Transport
Drosophila serpent protein
Propionates
3' Untranslated Regions
Electrophoretic Mobility Shift Assay
Cytoskeleton
Aspartic Acid
Hydroxyl Radical

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

In neurons, activity-dependent association of dendritically transported mRNA transcripts with the transacting factor CBF-A is mediated by A2RE/RTS elements. / Raju, Chandrasekhar S.; Fukuda, Nanaho; López-Iglesias, Carmen; Göritz, Christian; Visa, Neus; Percipalle, Piergiorgio.

In: Molecular Biology of the Cell, Vol. 22, No. 11, 01.06.2011, p. 1864-1877.

Research output: Contribution to journalArticle

Raju, Chandrasekhar S. ; Fukuda, Nanaho ; López-Iglesias, Carmen ; Göritz, Christian ; Visa, Neus ; Percipalle, Piergiorgio. / In neurons, activity-dependent association of dendritically transported mRNA transcripts with the transacting factor CBF-A is mediated by A2RE/RTS elements. In: Molecular Biology of the Cell. 2011 ; Vol. 22, No. 11. pp. 1864-1877.
@article{1791157c43eb444cbc9d91b9ee27bb98,
title = "In neurons, activity-dependent association of dendritically transported mRNA transcripts with the transacting factor CBF-A is mediated by A2RE/RTS elements",
abstract = "In neurons certain mRNA transcripts are transported to synapses through mechanisms that are not fully understood. Here we report that the heterogeneous nuclear ribonucleoprotein CBF-A (CArG Box binding Factor A) facilitates dendritic transport and localization of activity-regulated cytoskeleton- associated protein (Arc), brain-derived neurotrophic factor (BDNF), and calmodulin-dependent protein kinase II (CaMKIIα) mRNAs. We discovered that, in the adult mouse brain, CBF-A has a broad distribution. In the nucleus, CBF-A was found at active transcription sites and interchromosomal spaces and close to nuclear pores. In the cytoplasm, CBF-A localized to dendrites as well as pre- and postsynaptic sites. CBF-A was found in synaptosomal fractions, associated with Arc, BDNF, and CaMKIIα mRNAs. Electrophoretic mobility shift assays demonstrated a direct interaction mediated via their hnRNP A2 response element (A2RE)/RNA trafficking sequence (RTS) elements located in the 3′ untranslated regions. In situ hybridization and microscopy on live hippocampal neurons showed that CBF-A is in dynamic granules containing Arc, BDNF, and CaMKIIα mRNAs. N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) postsynaptic receptor stimulation led to CBF-A accumulation in dendrites; increased Arc, BDNF, and CaMKIIα mRNA levels; and increased amounts of transcripts coprecipitating with CBF-A. Finally, CBF-A gene knockdown led to decreased mRNA levels. We propose that CBF-A cotranscriptionally binds RTSs in Arc, BDNF, and CaMKIIα mRNAs and follows the transcripts from genes to dendrites, promoting activity-dependent nuclear sorting of transport-competent mRNAs.",
author = "Raju, {Chandrasekhar S.} and Nanaho Fukuda and Carmen L{\'o}pez-Iglesias and Christian G{\"o}ritz and Neus Visa and Piergiorgio Percipalle",
year = "2011",
month = "6",
day = "1",
doi = "10.1091/mbc.E10-11-0904",
language = "English (US)",
volume = "22",
pages = "1864--1877",
journal = "Molecular Biology of the Cell",
issn = "1059-1524",
publisher = "American Society for Cell Biology",
number = "11",

}

TY - JOUR

T1 - In neurons, activity-dependent association of dendritically transported mRNA transcripts with the transacting factor CBF-A is mediated by A2RE/RTS elements

AU - Raju, Chandrasekhar S.

AU - Fukuda, Nanaho

AU - López-Iglesias, Carmen

AU - Göritz, Christian

AU - Visa, Neus

AU - Percipalle, Piergiorgio

PY - 2011/6/1

Y1 - 2011/6/1

N2 - In neurons certain mRNA transcripts are transported to synapses through mechanisms that are not fully understood. Here we report that the heterogeneous nuclear ribonucleoprotein CBF-A (CArG Box binding Factor A) facilitates dendritic transport and localization of activity-regulated cytoskeleton- associated protein (Arc), brain-derived neurotrophic factor (BDNF), and calmodulin-dependent protein kinase II (CaMKIIα) mRNAs. We discovered that, in the adult mouse brain, CBF-A has a broad distribution. In the nucleus, CBF-A was found at active transcription sites and interchromosomal spaces and close to nuclear pores. In the cytoplasm, CBF-A localized to dendrites as well as pre- and postsynaptic sites. CBF-A was found in synaptosomal fractions, associated with Arc, BDNF, and CaMKIIα mRNAs. Electrophoretic mobility shift assays demonstrated a direct interaction mediated via their hnRNP A2 response element (A2RE)/RNA trafficking sequence (RTS) elements located in the 3′ untranslated regions. In situ hybridization and microscopy on live hippocampal neurons showed that CBF-A is in dynamic granules containing Arc, BDNF, and CaMKIIα mRNAs. N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) postsynaptic receptor stimulation led to CBF-A accumulation in dendrites; increased Arc, BDNF, and CaMKIIα mRNA levels; and increased amounts of transcripts coprecipitating with CBF-A. Finally, CBF-A gene knockdown led to decreased mRNA levels. We propose that CBF-A cotranscriptionally binds RTSs in Arc, BDNF, and CaMKIIα mRNAs and follows the transcripts from genes to dendrites, promoting activity-dependent nuclear sorting of transport-competent mRNAs.

AB - In neurons certain mRNA transcripts are transported to synapses through mechanisms that are not fully understood. Here we report that the heterogeneous nuclear ribonucleoprotein CBF-A (CArG Box binding Factor A) facilitates dendritic transport and localization of activity-regulated cytoskeleton- associated protein (Arc), brain-derived neurotrophic factor (BDNF), and calmodulin-dependent protein kinase II (CaMKIIα) mRNAs. We discovered that, in the adult mouse brain, CBF-A has a broad distribution. In the nucleus, CBF-A was found at active transcription sites and interchromosomal spaces and close to nuclear pores. In the cytoplasm, CBF-A localized to dendrites as well as pre- and postsynaptic sites. CBF-A was found in synaptosomal fractions, associated with Arc, BDNF, and CaMKIIα mRNAs. Electrophoretic mobility shift assays demonstrated a direct interaction mediated via their hnRNP A2 response element (A2RE)/RNA trafficking sequence (RTS) elements located in the 3′ untranslated regions. In situ hybridization and microscopy on live hippocampal neurons showed that CBF-A is in dynamic granules containing Arc, BDNF, and CaMKIIα mRNAs. N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) postsynaptic receptor stimulation led to CBF-A accumulation in dendrites; increased Arc, BDNF, and CaMKIIα mRNA levels; and increased amounts of transcripts coprecipitating with CBF-A. Finally, CBF-A gene knockdown led to decreased mRNA levels. We propose that CBF-A cotranscriptionally binds RTSs in Arc, BDNF, and CaMKIIα mRNAs and follows the transcripts from genes to dendrites, promoting activity-dependent nuclear sorting of transport-competent mRNAs.

UR - http://www.scopus.com/inward/record.url?scp=79957598473&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79957598473&partnerID=8YFLogxK

U2 - 10.1091/mbc.E10-11-0904

DO - 10.1091/mbc.E10-11-0904

M3 - Article

C2 - 21471000

AN - SCOPUS:79957598473

VL - 22

SP - 1864

EP - 1877

JO - Molecular Biology of the Cell

JF - Molecular Biology of the Cell

SN - 1059-1524

IS - 11

ER -