TY - JOUR
T1 - HuD regulates mRNA-circRNA-miRNA networks in the mouse striatum linked to neuronal development and drug addiction
AU - Dell’orco, Michela
AU - Elyaderani, Amir
AU - Vannan, Annika
AU - Sekar, Shobana
AU - Powell, Gregory
AU - Liang, Winnie S.
AU - Neisewander, Janet L.
AU - Perrone-Bizzozero, Nora I.
N1 - Funding Information:
Funding: This study was funded by NIH grant 1 R21 DA048651-01A1 to J.L.N. and N.I.P.-B.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/9
Y1 - 2021/9
N2 - 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.
AB - 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.
KW - CeRNAs
KW - CircRNAs
KW - ELAVL4
KW - HuD
KW - MiRNAs
KW - RNA-binding proteins
UR - http://www.scopus.com/inward/record.url?scp=85115704429&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85115704429&partnerID=8YFLogxK
U2 - 10.3390/biology10090939
DO - 10.3390/biology10090939
M3 - Article
AN - SCOPUS:85115704429
SN - 2079-7737
VL - 10
JO - Biology
JF - Biology
IS - 9
M1 - 939
ER -