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miR-212/132 expression and functions: within and beyond the neuronal compartment.

Wanet A, Tacheny A, Arnould T, Renard P - Nucleic Acids Res. (2012)

Bottom Line: Although their involvement in neuronal functions is the most described, evidences point towards a role of these miRNAs in many other biological processes, including inflammation and immune functions.Incidentally, miR-132 was recently classified as a 'neurimmiR', a class of miRNAs operating within and between the neural and immune compartments.In this review, we propose an outline of the current knowledge about miR-132 and miR-212 functions in neurons and immune cells, by describing the signalling pathways and transcription factors regulating their expression as well as their putative or demonstrated roles and validated mRNA targets.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (FUNDP), 61 rue de Bruxelles, 5000 Namur, Belgium.

ABSTRACT
During the last two decades, microRNAs (miRNAs) emerged as critical regulators of gene expression. By modulating the expression of numerous target mRNAs mainly at the post-transcriptional level, these small non-coding RNAs have been involved in most, if not all, biological processes as well as in the pathogenesis of a number of diseases. miR-132 and miR-212 are tandem miRNAs whose expression is necessary for the proper development, maturation and function of neurons and whose deregulation is associated with several neurological disorders, such as Alzheimer's disease and tauopathies (neurodegenerative diseases resulting from the pathological aggregation of tau protein in the human brain). Although their involvement in neuronal functions is the most described, evidences point towards a role of these miRNAs in many other biological processes, including inflammation and immune functions. Incidentally, miR-132 was recently classified as a 'neurimmiR', a class of miRNAs operating within and between the neural and immune compartments. In this review, we propose an outline of the current knowledge about miR-132 and miR-212 functions in neurons and immune cells, by describing the signalling pathways and transcription factors regulating their expression as well as their putative or demonstrated roles and validated mRNA targets.

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Related in: MedlinePlus

Inducers and targets of the miR-212/132 locus in the neuronal compartment. In neurons, the transcriptional repressor REST is targeted to proteolysis, enabling the transcription of its target genes. Various stimuli (such as the exposition to neurotrophins or photic cues, or an extended access to cocaine) lead to the transcription of the miR-212/132 locus through CREB activation, although an unidentified ERK1/2-dependent, MSK1/2- and CREB-independent mechanism may also contribute to miR-212/132 expression in BDNF-stimulated neurons (dashed arrow). Histone 3 post-translational modifications are also involved in pri-miR-212/132 expression following light exposure. By repressing the expression of several mRNA targets (AChE is a probable but not yet demonstrated target of miR-132 in neurons), miR-212/132 are involved in neurite outgrowth and dendrite morphology as well as in the resetting of the circadian clock, and would participate to synaptic functions by up-regulating the expression of the glutamate receptors NR2A, NR2B and GluR1. miR-132 expression deregulation is also associated with the development of tauopathies through the targeting of PTBP2. Besides, miR-212 would be involved in regulating the vulnerability to cocaine addiction by targeting Spred1 mRNA.
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gks151-F3: Inducers and targets of the miR-212/132 locus in the neuronal compartment. In neurons, the transcriptional repressor REST is targeted to proteolysis, enabling the transcription of its target genes. Various stimuli (such as the exposition to neurotrophins or photic cues, or an extended access to cocaine) lead to the transcription of the miR-212/132 locus through CREB activation, although an unidentified ERK1/2-dependent, MSK1/2- and CREB-independent mechanism may also contribute to miR-212/132 expression in BDNF-stimulated neurons (dashed arrow). Histone 3 post-translational modifications are also involved in pri-miR-212/132 expression following light exposure. By repressing the expression of several mRNA targets (AChE is a probable but not yet demonstrated target of miR-132 in neurons), miR-212/132 are involved in neurite outgrowth and dendrite morphology as well as in the resetting of the circadian clock, and would participate to synaptic functions by up-regulating the expression of the glutamate receptors NR2A, NR2B and GluR1. miR-132 expression deregulation is also associated with the development of tauopathies through the targeting of PTBP2. Besides, miR-212 would be involved in regulating the vulnerability to cocaine addiction by targeting Spred1 mRNA.

Mentions: Although only two transcription factors, REST and CREB, have been formally demonstrated to control the transcription of miR-212/132, other yet unidentified transcriptional regulators must be involved. Indeed, the deletion of the AK006051 transcript intron 1 nearly abolishes the expression of a luciferase reporter gene while the mutation of the three CRE sites localized in this particular intron only slightly reduces the induction of the luciferase following brain-derived neurotrophic factor (BDNF) stimulation (13). In addition, although BDNF-induced CREB-dependent miR-212/132 transcription has been shown to depend on extracellular signal-regulated kinases 1/2 (ERK1/2) activation and partly on mitogen- and stress-activated protein kinase 1/2 (MSK1/2) activation, an unidentified ERK1/2-dependent, MSK1/2- and CREB-independent mechanism may also contribute to miR-212/132 expression in BDNF-stimulated neurons (13) (Figure 3).Figure 3.


miR-212/132 expression and functions: within and beyond the neuronal compartment.

Wanet A, Tacheny A, Arnould T, Renard P - Nucleic Acids Res. (2012)

Inducers and targets of the miR-212/132 locus in the neuronal compartment. In neurons, the transcriptional repressor REST is targeted to proteolysis, enabling the transcription of its target genes. Various stimuli (such as the exposition to neurotrophins or photic cues, or an extended access to cocaine) lead to the transcription of the miR-212/132 locus through CREB activation, although an unidentified ERK1/2-dependent, MSK1/2- and CREB-independent mechanism may also contribute to miR-212/132 expression in BDNF-stimulated neurons (dashed arrow). Histone 3 post-translational modifications are also involved in pri-miR-212/132 expression following light exposure. By repressing the expression of several mRNA targets (AChE is a probable but not yet demonstrated target of miR-132 in neurons), miR-212/132 are involved in neurite outgrowth and dendrite morphology as well as in the resetting of the circadian clock, and would participate to synaptic functions by up-regulating the expression of the glutamate receptors NR2A, NR2B and GluR1. miR-132 expression deregulation is also associated with the development of tauopathies through the targeting of PTBP2. Besides, miR-212 would be involved in regulating the vulnerability to cocaine addiction by targeting Spred1 mRNA.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3367188&req=5

gks151-F3: Inducers and targets of the miR-212/132 locus in the neuronal compartment. In neurons, the transcriptional repressor REST is targeted to proteolysis, enabling the transcription of its target genes. Various stimuli (such as the exposition to neurotrophins or photic cues, or an extended access to cocaine) lead to the transcription of the miR-212/132 locus through CREB activation, although an unidentified ERK1/2-dependent, MSK1/2- and CREB-independent mechanism may also contribute to miR-212/132 expression in BDNF-stimulated neurons (dashed arrow). Histone 3 post-translational modifications are also involved in pri-miR-212/132 expression following light exposure. By repressing the expression of several mRNA targets (AChE is a probable but not yet demonstrated target of miR-132 in neurons), miR-212/132 are involved in neurite outgrowth and dendrite morphology as well as in the resetting of the circadian clock, and would participate to synaptic functions by up-regulating the expression of the glutamate receptors NR2A, NR2B and GluR1. miR-132 expression deregulation is also associated with the development of tauopathies through the targeting of PTBP2. Besides, miR-212 would be involved in regulating the vulnerability to cocaine addiction by targeting Spred1 mRNA.
Mentions: Although only two transcription factors, REST and CREB, have been formally demonstrated to control the transcription of miR-212/132, other yet unidentified transcriptional regulators must be involved. Indeed, the deletion of the AK006051 transcript intron 1 nearly abolishes the expression of a luciferase reporter gene while the mutation of the three CRE sites localized in this particular intron only slightly reduces the induction of the luciferase following brain-derived neurotrophic factor (BDNF) stimulation (13). In addition, although BDNF-induced CREB-dependent miR-212/132 transcription has been shown to depend on extracellular signal-regulated kinases 1/2 (ERK1/2) activation and partly on mitogen- and stress-activated protein kinase 1/2 (MSK1/2) activation, an unidentified ERK1/2-dependent, MSK1/2- and CREB-independent mechanism may also contribute to miR-212/132 expression in BDNF-stimulated neurons (13) (Figure 3).Figure 3.

Bottom Line: Although their involvement in neuronal functions is the most described, evidences point towards a role of these miRNAs in many other biological processes, including inflammation and immune functions.Incidentally, miR-132 was recently classified as a 'neurimmiR', a class of miRNAs operating within and between the neural and immune compartments.In this review, we propose an outline of the current knowledge about miR-132 and miR-212 functions in neurons and immune cells, by describing the signalling pathways and transcription factors regulating their expression as well as their putative or demonstrated roles and validated mRNA targets.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Biochemistry and Cell Biology (URBC), Namur Research Institute for Life Sciences (NARILIS), University of Namur (FUNDP), 61 rue de Bruxelles, 5000 Namur, Belgium.

ABSTRACT
During the last two decades, microRNAs (miRNAs) emerged as critical regulators of gene expression. By modulating the expression of numerous target mRNAs mainly at the post-transcriptional level, these small non-coding RNAs have been involved in most, if not all, biological processes as well as in the pathogenesis of a number of diseases. miR-132 and miR-212 are tandem miRNAs whose expression is necessary for the proper development, maturation and function of neurons and whose deregulation is associated with several neurological disorders, such as Alzheimer's disease and tauopathies (neurodegenerative diseases resulting from the pathological aggregation of tau protein in the human brain). Although their involvement in neuronal functions is the most described, evidences point towards a role of these miRNAs in many other biological processes, including inflammation and immune functions. Incidentally, miR-132 was recently classified as a 'neurimmiR', a class of miRNAs operating within and between the neural and immune compartments. In this review, we propose an outline of the current knowledge about miR-132 and miR-212 functions in neurons and immune cells, by describing the signalling pathways and transcription factors regulating their expression as well as their putative or demonstrated roles and validated mRNA targets.

Show MeSH
Related in: MedlinePlus