Long 3'UTR of Nurr1 mRNAs is targeted by miRNAs in mesencephalic dopamine neurons

The development of mesencephalic dopamine neurons and their survival later in life requires the continuous presence of the transcription factor Nurr1 (NR4A2). Nurr1 belongs to the nuclear receptors superfamily. However, it is an orphan member that does not require a ligand to regulate the transcript...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2017-11, Vol.12 (11), p.e0188177-e0188177
Main Authors: Pereira, Luis Alberto, Munita, Roberto, González, Marcela Paz, Andrés, María Estela
Format: Article
Language:English
Subjects:
3' Untranslated regions
Analysis
Basic Medicine
Bioinformatics
Biology and life sciences
Cancer
Cell survival
Control
Dopamine
Gene expression
Genetic aspects
Genomes
Kinases
Ligands
Medical and Health Sciences
Medicin och hälsovetenskap
Medicine and Health Sciences
Medicinska och farmaceutiska grundvetenskaper
Mesencephalon
Messenger RNA
MicroRNA
MicroRNAs
miRNA
Molecular biology
Neurons
Neurosciences
Neurovetenskaper
Nuclear receptors
Nurr1 protein
Physical Sciences
Physiological aspects
Receptors
Research and Analysis Methods
Rodents
Splicing
Transcription factors
Transfection
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The development of mesencephalic dopamine neurons and their survival later in life requires the continuous presence of the transcription factor Nurr1 (NR4A2). Nurr1 belongs to the nuclear receptors superfamily. However, it is an orphan member that does not require a ligand to regulate the transcription of its target genes. Therefore, controlling the expression of Nurr1 is an important manner to control its function. Several reports have shown that microRNAs (miRNAs) regulate Nurr1 expression. However, Nurr1 has several splicing variants, posing the question what variants are subjected to miRNA regulation. In this work, we identified a long 3'UTR variant of rat Nurr1 mRNA. We used bioinformatics analysis to identify miRNAs with the potential to regulate Nurr1 expression. Reporter assays performed with the luciferase gene fused to the short (658 bp) or long (1,339 bp) 3'UTR of rat Nurr1 mRNAs, showed that miR-93, miR-204 and miR-302d selectively regulate the mRNA with the longest 3'UTR. We found that the longest variant of Nurr1 mRNA expresses in the rat mesencephalon as assessed by PCR. The transfection of rat mesencephalic neurons with mixed miR-93, miR-204 and miR-302d resulted in a significant reduction of Nurr1 protein levels. In conclusion, Nurr1 mRNA variant with the longest 3'UTR undergoes a specific regulation by miRNAs. It is discussed the importance of fine-tuning Nurr1 protein levels in mesencephalic dopamine neurons.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0188177