TY - JOUR
T1 - MicroRNAs
T2 - Meta-controllers of gene expression in synaptic activity emerge as genetic and diagnostic markers of human disease
AU - Ceman, Stephanie
AU - Saugstad, Julie
N1 - Funding Information:
We thank Dr. Michael Roberts for his comments and superb editing which greatly improved this manuscript, the NIH for generous support by grants R21NS054220 and R01NS064270 (JAS) and the Spastic Paralysis Research Foundation of the Illinois-Eastern Iowa District of Kiwanis International for a grant [SC].
PY - 2011/4
Y1 - 2011/4
N2 - MicroRNAs are members of the non-protein-coding family of RNAs. They serve as regulators of gene expression by modulating the translation and/or stability of messenger RNA targets. The discovery of microRNAs has revolutionized the field of cell biology, and has permanently altered the prevailing view of a linear relationship between gene and protein expression. The increased complexity of gene regulation is both exciting and daunting, as emerging evidence supports a pervasive role for microRNAs in virtually every cellular process. This review briefly describes microRNA processing and formation of RNA-induced silencing complexes, with a focus on the role of RNA binding proteins in this process. We also discuss mechanisms for microRNA-mediated regulation of translation, particularly in dendritic spine formation and function, and the role of microRNAs in synaptic plasticity. We then discuss the evidence for altered microRNA function in cognitive brain disorders, and the effect of gene mutations revealed by single nucleotide polymorphism analysis on altered microRNA function and human disease. Further, we present evidence that altered microRNA expression in circulating fluids such as plasma/serum can correlate with, and serve as, novel diagnostic biomarkers of human disease.
AB - MicroRNAs are members of the non-protein-coding family of RNAs. They serve as regulators of gene expression by modulating the translation and/or stability of messenger RNA targets. The discovery of microRNAs has revolutionized the field of cell biology, and has permanently altered the prevailing view of a linear relationship between gene and protein expression. The increased complexity of gene regulation is both exciting and daunting, as emerging evidence supports a pervasive role for microRNAs in virtually every cellular process. This review briefly describes microRNA processing and formation of RNA-induced silencing complexes, with a focus on the role of RNA binding proteins in this process. We also discuss mechanisms for microRNA-mediated regulation of translation, particularly in dendritic spine formation and function, and the role of microRNAs in synaptic plasticity. We then discuss the evidence for altered microRNA function in cognitive brain disorders, and the effect of gene mutations revealed by single nucleotide polymorphism analysis on altered microRNA function and human disease. Further, we present evidence that altered microRNA expression in circulating fluids such as plasma/serum can correlate with, and serve as, novel diagnostic biomarkers of human disease.
KW - 3' untranslated region
KW - Brain disorders
KW - Dendrite
KW - Diagnostic marker
KW - Eukaryotic initiation factor
KW - Fragile X mental retardation protein
KW - Human disease
KW - MicroRNA
KW - Plasticity
KW - RNA binding protein
KW - RNA-induced silencing complex
KW - Single nucleotide polymorphism
KW - Translation
KW - mRNA stability
UR - http://www.scopus.com/inward/record.url?scp=79951850975&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79951850975&partnerID=8YFLogxK
U2 - 10.1016/j.pharmthera.2011.01.004
DO - 10.1016/j.pharmthera.2011.01.004
M3 - Review article
C2 - 21256154
AN - SCOPUS:79951850975
VL - 130
SP - 26
EP - 37
JO - Pharmacology and Therapeutics, Part A: Chemotherapy, Toxicology and
JF - Pharmacology and Therapeutics, Part A: Chemotherapy, Toxicology and
SN - 0163-7258
IS - 1
ER -