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From Genetics to Epigenetics: New Perspectives in Tourette Syndrome Research.

Pagliaroli L, Vető B, Arányi T, Barta C - Front Neurosci (2016)

Bottom Line: Epigenetic regulation has been shown to have an impact in the development of many neuropsychiatric disorders, however very little is known about its effects on Tourette Syndrome.Epigenetic studies in other neurological and psychiatric disorders are discussed along with the TS-related epigenetic findings available in the literature to date.Moreover, we are proposing that some general epigenetic mechanisms seen in other neuropsychiatric disorders may also play a role in the pathogenesis of TS.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis UniversityBudapest, Hungary; Research Centre for Natural Sciences, Institute of Enzymology, Hungarian Academy of SciencesBudapest, Hungary.

ABSTRACT
Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder marked by the appearance of multiple involuntary motor and vocal tics. TS presents high comorbidity rates with other disorders such as attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). TS is highly heritable and has a complex polygenic background. However, environmental factors also play a role in the manifestation of symptoms. Different epigenetic mechanisms may represent the link between these two causalities. Epigenetic regulation has been shown to have an impact in the development of many neuropsychiatric disorders, however very little is known about its effects on Tourette Syndrome. This review provides a summary of the recent findings in genetic background of TS, followed by an overview on different epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs in the regulation of gene expression. Epigenetic studies in other neurological and psychiatric disorders are discussed along with the TS-related epigenetic findings available in the literature to date. Moreover, we are proposing that some general epigenetic mechanisms seen in other neuropsychiatric disorders may also play a role in the pathogenesis of TS.

No MeSH data available.


Related in: MedlinePlus

miRNA biogenesis. MicroRNA (miRNA) genes are transcribed as primary miRNAs (pri-miRNAs) by RNA polymerase II (Pol II) in the nucleus. The long pri-miRNAs are cleaved by Microprocessor, which includes DROSHA and DiGeorge syndrome critical region 8 (DGCR8), to produce precursor miRNAs (pre-miRNAs), which are then exported to the cytoplasm by Exportin 5 and further processed by the DICER/TRPB complex to produce an miRNA duplex. One strand of the mature miRNA (the guide strand) is loaded into the miRNA-induced silencing complex (RISC) mediating gene suppression by targeted mRNA degradation or translational repression.
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Figure 3: miRNA biogenesis. MicroRNA (miRNA) genes are transcribed as primary miRNAs (pri-miRNAs) by RNA polymerase II (Pol II) in the nucleus. The long pri-miRNAs are cleaved by Microprocessor, which includes DROSHA and DiGeorge syndrome critical region 8 (DGCR8), to produce precursor miRNAs (pre-miRNAs), which are then exported to the cytoplasm by Exportin 5 and further processed by the DICER/TRPB complex to produce an miRNA duplex. One strand of the mature miRNA (the guide strand) is loaded into the miRNA-induced silencing complex (RISC) mediating gene suppression by targeted mRNA degradation or translational repression.

Mentions: The biogenesis of microRNA involves two different cleavage steps by protein complexes taking place in the nucleus and in the cytoplasm leading to the development of an ~22 nucleotide long mature single-stranded miRNA (Figure 3; Filipowicz et al., 2008). First, the gene coding for miRNAs is transcribed by RNA Polimerase II resulting in a long precursor pri-miRNA characterized by a hairpin or fold-back structure with an imperfectly base-paired stem and a terminal loop (Miyoshi et al., 2010). Then, the hairpin structure of the pri-miRNA is cleaved and the ~70 nucleotide long precursor called pre-miRNA is released (Miyoshi et al., 2010). Subsequently, the pre-miRNA is exported into the cytoplasm (Kim et al., 2009). Once in the cytoplasm, the pre-miRNA is processed by RNase III Dicer generating a ~22 nucleotide miRNA-miRNA*duplex. One strand of the duplex is loaded into a large multi-protein miRNA ribonucleoprotein complex (RISC complex), while the other strand, “passenger,” is degraded. Once incorporated into RISC, the miRNA guides the complex to its messenger RNA targets by base-pairing interactions. The binding to the miRNA target relies on the seed sequence, a 6–8 nucleotide domain located at the 5′ end of the miRNA. Based on the complementarity of the seed sequence and the target mRNA sequence located in the 3′UTRof the transcript, miRNAs down-regulate gene expression either through translational repression or mRNA degradation (Hutvágner and Zamore, 2002).


From Genetics to Epigenetics: New Perspectives in Tourette Syndrome Research.

Pagliaroli L, Vető B, Arányi T, Barta C - Front Neurosci (2016)

miRNA biogenesis. MicroRNA (miRNA) genes are transcribed as primary miRNAs (pri-miRNAs) by RNA polymerase II (Pol II) in the nucleus. The long pri-miRNAs are cleaved by Microprocessor, which includes DROSHA and DiGeorge syndrome critical region 8 (DGCR8), to produce precursor miRNAs (pre-miRNAs), which are then exported to the cytoplasm by Exportin 5 and further processed by the DICER/TRPB complex to produce an miRNA duplex. One strand of the mature miRNA (the guide strand) is loaded into the miRNA-induced silencing complex (RISC) mediating gene suppression by targeted mRNA degradation or translational repression.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4940402&req=5

Figure 3: miRNA biogenesis. MicroRNA (miRNA) genes are transcribed as primary miRNAs (pri-miRNAs) by RNA polymerase II (Pol II) in the nucleus. The long pri-miRNAs are cleaved by Microprocessor, which includes DROSHA and DiGeorge syndrome critical region 8 (DGCR8), to produce precursor miRNAs (pre-miRNAs), which are then exported to the cytoplasm by Exportin 5 and further processed by the DICER/TRPB complex to produce an miRNA duplex. One strand of the mature miRNA (the guide strand) is loaded into the miRNA-induced silencing complex (RISC) mediating gene suppression by targeted mRNA degradation or translational repression.
Mentions: The biogenesis of microRNA involves two different cleavage steps by protein complexes taking place in the nucleus and in the cytoplasm leading to the development of an ~22 nucleotide long mature single-stranded miRNA (Figure 3; Filipowicz et al., 2008). First, the gene coding for miRNAs is transcribed by RNA Polimerase II resulting in a long precursor pri-miRNA characterized by a hairpin or fold-back structure with an imperfectly base-paired stem and a terminal loop (Miyoshi et al., 2010). Then, the hairpin structure of the pri-miRNA is cleaved and the ~70 nucleotide long precursor called pre-miRNA is released (Miyoshi et al., 2010). Subsequently, the pre-miRNA is exported into the cytoplasm (Kim et al., 2009). Once in the cytoplasm, the pre-miRNA is processed by RNase III Dicer generating a ~22 nucleotide miRNA-miRNA*duplex. One strand of the duplex is loaded into a large multi-protein miRNA ribonucleoprotein complex (RISC complex), while the other strand, “passenger,” is degraded. Once incorporated into RISC, the miRNA guides the complex to its messenger RNA targets by base-pairing interactions. The binding to the miRNA target relies on the seed sequence, a 6–8 nucleotide domain located at the 5′ end of the miRNA. Based on the complementarity of the seed sequence and the target mRNA sequence located in the 3′UTRof the transcript, miRNAs down-regulate gene expression either through translational repression or mRNA degradation (Hutvágner and Zamore, 2002).

Bottom Line: Epigenetic regulation has been shown to have an impact in the development of many neuropsychiatric disorders, however very little is known about its effects on Tourette Syndrome.Epigenetic studies in other neurological and psychiatric disorders are discussed along with the TS-related epigenetic findings available in the literature to date.Moreover, we are proposing that some general epigenetic mechanisms seen in other neuropsychiatric disorders may also play a role in the pathogenesis of TS.

View Article: PubMed Central - PubMed

Affiliation: Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis UniversityBudapest, Hungary; Research Centre for Natural Sciences, Institute of Enzymology, Hungarian Academy of SciencesBudapest, Hungary.

ABSTRACT
Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder marked by the appearance of multiple involuntary motor and vocal tics. TS presents high comorbidity rates with other disorders such as attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). TS is highly heritable and has a complex polygenic background. However, environmental factors also play a role in the manifestation of symptoms. Different epigenetic mechanisms may represent the link between these two causalities. Epigenetic regulation has been shown to have an impact in the development of many neuropsychiatric disorders, however very little is known about its effects on Tourette Syndrome. This review provides a summary of the recent findings in genetic background of TS, followed by an overview on different epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNAs in the regulation of gene expression. Epigenetic studies in other neurological and psychiatric disorders are discussed along with the TS-related epigenetic findings available in the literature to date. Moreover, we are proposing that some general epigenetic mechanisms seen in other neuropsychiatric disorders may also play a role in the pathogenesis of TS.

No MeSH data available.


Related in: MedlinePlus