HuD Regulates mRNA-circRNA-miRNA Networks in the Mouse Striatum Linked to Neuronal Development and Drug Addiction
The RNA-binding protein HuD (a.k.a., ELAVL4) is involved in neuronal development and synaptic plasticity mechanisms, including addiction-related processes such as cocaine conditioned-place preference (CPP) and food reward. The most studied function of this protein is mRNA stabilization; however, we...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | Biology |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2079-7737/10/9/939 |
| _version_ | 1797520193191149568 |
|---|---|
| author | Michela Dell’Orco Amir Elyaderani Annika Vannan Shobana Sekar Gregory Powell Winnie S. Liang Janet L. Neisewander Nora I. Perrone-Bizzozero |
| author_facet | Michela Dell’Orco Amir Elyaderani Annika Vannan Shobana Sekar Gregory Powell Winnie S. Liang Janet L. Neisewander Nora I. Perrone-Bizzozero |
| author_sort | Michela Dell’Orco |
| collection | DOAJ |
| description | The RNA-binding protein HuD (a.k.a., ELAVL4) is involved in neuronal development and synaptic plasticity mechanisms, including addiction-related processes such as cocaine conditioned-place preference (CPP) and food reward. The most studied function of this protein is mRNA stabilization; however, we have recently shown that HuD also regulates the levels of circular RNAs (circRNAs) in neurons. To examine the role of HuD in the control of coding and non-coding RNA networks associated with substance use, we identified sets of differentially expressed mRNAs, circRNAs and miRNAs in the striatum of HuD knockout (KO) mice. Our findings indicate that significantly downregulated mRNAs are enriched in biological pathways related to cell morphology and behavior. Furthermore, deletion of HuD altered the levels of 15 miRNAs associated with drug seeking. Using these sets of data, we predicted that a large number of upregulated miRNAs form competing endogenous RNA (ceRNA) networks with circRNAs and mRNAs associated with the neuronal development and synaptic plasticity proteins LSAMP and MARK3. Additionally, several downregulated miRNAs form ceRNA networks with mRNAs and circRNAs from MEF2D, PIK3R3, PTRPM and other neuronal proteins. Together, our results indicate that HuD regulates ceRNA networks controlling the levels of mRNAs associated with neuronal differentiation and synaptic physiology. |
| first_indexed | 2024-03-10T07:53:23Z |
| format | Article |
| id | doaj.art-8438b904481540978b037c8cec99c614 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T07:53:23Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-8438b904481540978b037c8cec99c6142023-11-22T12:06:34ZengMDPI AGBiology2079-77372021-09-0110993910.3390/biology10090939HuD Regulates mRNA-circRNA-miRNA Networks in the Mouse Striatum Linked to Neuronal Development and Drug AddictionMichela Dell’Orco0Amir Elyaderani1Annika Vannan2Shobana Sekar3Gregory Powell4Winnie S. Liang5Janet L. Neisewander6Nora I. Perrone-Bizzozero7Department of Neurosciences, University of New Mexico Health Science Center, University of New Mexico, Albuquerque, NM 87131, USANeurogenomics Division, Translational Genomics Research Institute, 445 N. Fifth Street, Phoenix, AZ 85004, USASchool of Life Sciences, Arizona State University, Tempe, AZ 85287, USANeurogenomics Division, Translational Genomics Research Institute, 445 N. Fifth Street, Phoenix, AZ 85004, USASchool of Life Sciences, Arizona State University, Tempe, AZ 85287, USANeurogenomics Division, Translational Genomics Research Institute, 445 N. Fifth Street, Phoenix, AZ 85004, USASchool of Life Sciences, Arizona State University, Tempe, AZ 85287, USADepartment of Neurosciences, University of New Mexico Health Science Center, University of New Mexico, Albuquerque, NM 87131, USAThe RNA-binding protein HuD (a.k.a., ELAVL4) is involved in neuronal development and synaptic plasticity mechanisms, including addiction-related processes such as cocaine conditioned-place preference (CPP) and food reward. The most studied function of this protein is mRNA stabilization; however, we have recently shown that HuD also regulates the levels of circular RNAs (circRNAs) in neurons. To examine the role of HuD in the control of coding and non-coding RNA networks associated with substance use, we identified sets of differentially expressed mRNAs, circRNAs and miRNAs in the striatum of HuD knockout (KO) mice. Our findings indicate that significantly downregulated mRNAs are enriched in biological pathways related to cell morphology and behavior. Furthermore, deletion of HuD altered the levels of 15 miRNAs associated with drug seeking. Using these sets of data, we predicted that a large number of upregulated miRNAs form competing endogenous RNA (ceRNA) networks with circRNAs and mRNAs associated with the neuronal development and synaptic plasticity proteins LSAMP and MARK3. Additionally, several downregulated miRNAs form ceRNA networks with mRNAs and circRNAs from MEF2D, PIK3R3, PTRPM and other neuronal proteins. Together, our results indicate that HuD regulates ceRNA networks controlling the levels of mRNAs associated with neuronal differentiation and synaptic physiology.https://www.mdpi.com/2079-7737/10/9/939RNA-binding proteinsmiRNAscircRNAsceRNAsHuDELAVL4 |
| spellingShingle | Michela Dell’Orco Amir Elyaderani Annika Vannan Shobana Sekar Gregory Powell Winnie S. Liang Janet L. Neisewander Nora I. Perrone-Bizzozero HuD Regulates mRNA-circRNA-miRNA Networks in the Mouse Striatum Linked to Neuronal Development and Drug Addiction Biology RNA-binding proteins miRNAs circRNAs ceRNAs HuD ELAVL4 |
| title | HuD Regulates mRNA-circRNA-miRNA Networks in the Mouse Striatum Linked to Neuronal Development and Drug Addiction |
| title_full | HuD Regulates mRNA-circRNA-miRNA Networks in the Mouse Striatum Linked to Neuronal Development and Drug Addiction |
| title_fullStr | HuD Regulates mRNA-circRNA-miRNA Networks in the Mouse Striatum Linked to Neuronal Development and Drug Addiction |
| title_full_unstemmed | HuD Regulates mRNA-circRNA-miRNA Networks in the Mouse Striatum Linked to Neuronal Development and Drug Addiction |
| title_short | HuD Regulates mRNA-circRNA-miRNA Networks in the Mouse Striatum Linked to Neuronal Development and Drug Addiction |
| title_sort | hud regulates mrna circrna mirna networks in the mouse striatum linked to neuronal development and drug addiction |
| topic | RNA-binding proteins miRNAs circRNAs ceRNAs HuD ELAVL4 |
| url | https://www.mdpi.com/2079-7737/10/9/939 |
| work_keys_str_mv | AT micheladellorco hudregulatesmrnacircrnamirnanetworksinthemousestriatumlinkedtoneuronaldevelopmentanddrugaddiction AT amirelyaderani hudregulatesmrnacircrnamirnanetworksinthemousestriatumlinkedtoneuronaldevelopmentanddrugaddiction AT annikavannan hudregulatesmrnacircrnamirnanetworksinthemousestriatumlinkedtoneuronaldevelopmentanddrugaddiction AT shobanasekar hudregulatesmrnacircrnamirnanetworksinthemousestriatumlinkedtoneuronaldevelopmentanddrugaddiction AT gregorypowell hudregulatesmrnacircrnamirnanetworksinthemousestriatumlinkedtoneuronaldevelopmentanddrugaddiction AT winniesliang hudregulatesmrnacircrnamirnanetworksinthemousestriatumlinkedtoneuronaldevelopmentanddrugaddiction AT janetlneisewander hudregulatesmrnacircrnamirnanetworksinthemousestriatumlinkedtoneuronaldevelopmentanddrugaddiction AT noraiperronebizzozero hudregulatesmrnacircrnamirnanetworksinthemousestriatumlinkedtoneuronaldevelopmentanddrugaddiction |