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Hypothalamic miRNAs: emerging roles in energy balance control.

Schneeberger M, Gomez-Valadés AG, Ramirez S, Gomis R, Claret M - Front Neurosci (2015)

Bottom Line: However, the mechanisms regulating these neuronal gene programmes in physiology and pathophysiology are not completely understood.MicroRNAs (miRNAs) are key regulators of gene expression that recently emerged as pivotal modulators of systemic metabolism.In this article we will review current evidence indicating that miRNAs in hypothalamic neurons are also implicated in appetite and whole-body energy balance control.

View Article: PubMed Central - PubMed

Affiliation: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona, Spain ; Department of Endocrinology and Nutrition, School of Medicine, Hospital Clínic, University of Barcelona Barcelona, Spain ; CIBER de Diabetes y Enfermedades Metabólicas Asociadas Barcelona, Spain.

ABSTRACT
The hypothalamus is a crucial central nervous system area controlling appetite, body weight and metabolism. It consists in multiple neuronal types that sense, integrate and generate appropriate responses to hormonal and nutritional signals partly by fine-tuning the expression of specific batteries of genes. However, the mechanisms regulating these neuronal gene programmes in physiology and pathophysiology are not completely understood. MicroRNAs (miRNAs) are key regulators of gene expression that recently emerged as pivotal modulators of systemic metabolism. In this article we will review current evidence indicating that miRNAs in hypothalamic neurons are also implicated in appetite and whole-body energy balance control.

No MeSH data available.


Related in: MedlinePlus

Canonical miRNA biogenesis. Schematic representation of the Dicer-dependent miRNA generation pathway. miRNA genes are transcribed by RNA polymerase II, followed by nuclear processing by the microprocessor complex (consitituted by DGCR8 and Drosha), cytoplasmatic export by Exportin 5 and Dicer-mediated processing. The miRNA duplex is then released and loaded into the RISC. The “passenger” strand is degraded and the so-called “guide” miRNA will interact with the target mRNA causing translational repression or degradation.
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Figure 1: Canonical miRNA biogenesis. Schematic representation of the Dicer-dependent miRNA generation pathway. miRNA genes are transcribed by RNA polymerase II, followed by nuclear processing by the microprocessor complex (consitituted by DGCR8 and Drosha), cytoplasmatic export by Exportin 5 and Dicer-mediated processing. The miRNA duplex is then released and loaded into the RISC. The “passenger” strand is degraded and the so-called “guide” miRNA will interact with the target mRNA causing translational repression or degradation.

Mentions: The majority of miRNAs are generated through a canonical process (Figure 1) (Ha and Kim, 2014). miRNA genes are transcribed by RNA polymerase II as long primary transcripts which contain a hairpin structure where miRNA sequences are encoded (pri-miRNA). Pri-miRNAs undergo nuclear processing by the Microprocessor complex (comprising Drosha and DGCR8), producing stem-loop precursors (pre-miRNAs). These pre-miRNAs will be exported to the cytoplasm and further processed by a complex containing the evolutionary conserved RNAse III-type endonuclease Dicer. Dicer cleaves the pre-miRNA terminal loop releasing a small RNA duplex, which is subsequently loaded into the RNA-induced silencing complex (RISC) (Ha and Kim, 2014). In general terms, miRNAs interact with the 3′ UTR region of target mRNAs causing its degradation and/or repression of protein translation (Figure 1) (Fabian et al., 2010).


Hypothalamic miRNAs: emerging roles in energy balance control.

Schneeberger M, Gomez-Valadés AG, Ramirez S, Gomis R, Claret M - Front Neurosci (2015)

Canonical miRNA biogenesis. Schematic representation of the Dicer-dependent miRNA generation pathway. miRNA genes are transcribed by RNA polymerase II, followed by nuclear processing by the microprocessor complex (consitituted by DGCR8 and Drosha), cytoplasmatic export by Exportin 5 and Dicer-mediated processing. The miRNA duplex is then released and loaded into the RISC. The “passenger” strand is degraded and the so-called “guide” miRNA will interact with the target mRNA causing translational repression or degradation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325937&req=5

Figure 1: Canonical miRNA biogenesis. Schematic representation of the Dicer-dependent miRNA generation pathway. miRNA genes are transcribed by RNA polymerase II, followed by nuclear processing by the microprocessor complex (consitituted by DGCR8 and Drosha), cytoplasmatic export by Exportin 5 and Dicer-mediated processing. The miRNA duplex is then released and loaded into the RISC. The “passenger” strand is degraded and the so-called “guide” miRNA will interact with the target mRNA causing translational repression or degradation.
Mentions: The majority of miRNAs are generated through a canonical process (Figure 1) (Ha and Kim, 2014). miRNA genes are transcribed by RNA polymerase II as long primary transcripts which contain a hairpin structure where miRNA sequences are encoded (pri-miRNA). Pri-miRNAs undergo nuclear processing by the Microprocessor complex (comprising Drosha and DGCR8), producing stem-loop precursors (pre-miRNAs). These pre-miRNAs will be exported to the cytoplasm and further processed by a complex containing the evolutionary conserved RNAse III-type endonuclease Dicer. Dicer cleaves the pre-miRNA terminal loop releasing a small RNA duplex, which is subsequently loaded into the RNA-induced silencing complex (RISC) (Ha and Kim, 2014). In general terms, miRNAs interact with the 3′ UTR region of target mRNAs causing its degradation and/or repression of protein translation (Figure 1) (Fabian et al., 2010).

Bottom Line: However, the mechanisms regulating these neuronal gene programmes in physiology and pathophysiology are not completely understood.MicroRNAs (miRNAs) are key regulators of gene expression that recently emerged as pivotal modulators of systemic metabolism.In this article we will review current evidence indicating that miRNAs in hypothalamic neurons are also implicated in appetite and whole-body energy balance control.

View Article: PubMed Central - PubMed

Affiliation: Diabetes and Obesity Research Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer Barcelona, Spain ; Department of Endocrinology and Nutrition, School of Medicine, Hospital Clínic, University of Barcelona Barcelona, Spain ; CIBER de Diabetes y Enfermedades Metabólicas Asociadas Barcelona, Spain.

ABSTRACT
The hypothalamus is a crucial central nervous system area controlling appetite, body weight and metabolism. It consists in multiple neuronal types that sense, integrate and generate appropriate responses to hormonal and nutritional signals partly by fine-tuning the expression of specific batteries of genes. However, the mechanisms regulating these neuronal gene programmes in physiology and pathophysiology are not completely understood. MicroRNAs (miRNAs) are key regulators of gene expression that recently emerged as pivotal modulators of systemic metabolism. In this article we will review current evidence indicating that miRNAs in hypothalamic neurons are also implicated in appetite and whole-body energy balance control.

No MeSH data available.


Related in: MedlinePlus