EMAIL THIS PAGE TO A FRIEND

The Journal of neuroscience : the official journal of the Society for Neuroscience

Dysregulated RNA-Induced Silencing Complex (RISC) Assembly within CNS Corresponds with Abnormal miRNA Expression during Autoimmune Demyelination.


PMID 25972178

Abstract

MicroRNAs (miRNAs) associate with Argonaute (Ago), GW182, and FXR1 proteins to form RNA-induced silencing complexes (RISCs). RISCs represent a critical checkpoint in the regulation and bioavailability of miRNAs. Recent studies have revealed dysregulation of miRNAs in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE); however, the function of RISCs in EAE and MS is largely unknown. Here, we examined the expression of Ago, GW182, and FXR1 in CNS tissue, oligodendrocytes (OLs), brain-infiltrating T lymphocytes, and CD3(+)splenocytes (SCs) of EAE mic, and found that global RISC protein levels were significantly dysregulated. Specifically, Ago2 and FXR1 levels were decreased in OLs and brain-infiltrating T cells in EAE mice. Accordingly, assembly of Ago2/GW182/FXR1 complexes in EAE brain tissues was disrupted, as confirmed by immunoprecipitation experiments. In parallel with alterations in RISC complex content in OLs, we found downregulation of miRNAs essential for differentiation and survival of OLs and myelin synthesis. In brain-infiltrating T lymphocytes, aberrant RISC formation contributed to miRNA-dependent proinflammatory helper T-cell polarization. In CD3(+) SCs, we found increased expression of both Ago2 and FXR1 in EAE compared with nonimmunized mice. Therefore, our results demonstrate a gradient in expression of miRNA between primary activated T cells in the periphery and polarized CNS-infiltrating T cells. These results suggest that, in polarized autoreactive effector T cells, miRNA synthesis is inhibited in response to dysregulated RISC assembly, allowing these cells to maintain a highly specific proinflammatory program. Therefore, our findings may provide a mechanism that leads to miRNA dysregulation in EAE/MS.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB1306339
ANTI-AGO1(N-TERMINAL) antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
HPA048342
Anti-AGO3 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2500346
Anti-EIF2C1 antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB2104940
Anti-EIF2C1, (N-terminal) antibody produced in rabbit, affinity isolated antibody
SAB1303264
ANTI-EIF2C2 (N-TERM) antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
SAB2107340
Anti-EIF2C3 antibody produced in rabbit, affinity isolated antibody
SAB1410321
Anti-EIF2C3 antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB2104518
Anti-EIF2C3, (N-terminal) antibody produced in rabbit, affinity isolated antibody
SAB2104338
Anti-EIF2C4 antibody produced in rabbit, affinity isolated antibody
SAB2500434
Anti-FXR1 antibody produced in goat, affinity isolated antibody, buffered aqueous solution
SAB2701659
Anti-fxr1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
HPA018246
Anti-FXR1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
AV40288
Anti-FXR1 antibody produced in rabbit, affinity isolated antibody
G5922
Anti-GW182 antibody produced in rabbit, ~1.0 mg/mL, affinity isolated antibody, buffered aqueous solution
SAB1401236
Anti-MAG antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA012499
Anti-MAG antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
HPA015305
Anti-TNRC6A antibody produced in rabbit, Ab1, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
HPA017869
Anti-TNRC6A antibody produced in rabbit, Ab2, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB2102506
Anti-TNRC6A antibody produced in rabbit, affinity isolated antibody
SAB4200084
Monoclonal Anti-AGO1 antibody produced in rat, ~1 mg/mL, clone 4B8, purified immunoglobulin
SAB4200085
Monoclonal Anti-AGO2 antibody produced in rat, ~1.5 mg/mL, clone 11A9, purified immunoglobulin
WH0027161M1
Monoclonal Anti-EIF2C2 antibody produced in mouse, clone 2E12-1C9, purified immunoglobulin, buffered aqueous solution
SAB1405034
Monoclonal Anti-EIF2C2 antibody produced in mouse, clone 4D1-1D1, purified immunoglobulin, buffered aqueous solution
SAB1402040 Monoclonal Anti-EIF2C4 antibody produced in mouse, clone 4G3, purified immunoglobulin, buffered aqueous solution
WH0008087M1
Monoclonal Anti-FXR1 antibody produced in mouse, clone 2G11, purified immunoglobulin, buffered aqueous solution
SAB1402258
Monoclonal Anti-MAG antibody produced in mouse, clone 3C7, purified immunoglobulin, buffered aqueous solution