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RNA Editing — Systemic Relevance and Clue to Disease Mechanisms?

View Article: PubMed Central - PubMed

ABSTRACT

Recent advances in sequencing technologies led to the identification of a plethora of different genes and several hundreds of amino acid recoding edited positions. Changes in editing rates of some of these positions were associated with diseases such as atherosclerosis, myopathy, epilepsy, major depression disorder, schizophrenia and other mental disorders as well as cancer and brain tumors. This review article summarizes our current knowledge on that front and presents glycine receptor C-to-U RNA editing as a first example of disease-associated increased RNA editing that includes assessment of disease mechanisms of the corresponding gene product in an animal model.

No MeSH data available.


Pathophysiological implications of altered ADAR-dependent RNA editing in disease. Both up- and down-regulation of A-to-I RNA editing (indicated by orange and blue colors, respectively) were associated with several, different diseases. Note that up-regulation of GABAAR α3 RNA editing makes an exception as it plays a role in development (indicated by gray text color).
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Figure 2: Pathophysiological implications of altered ADAR-dependent RNA editing in disease. Both up- and down-regulation of A-to-I RNA editing (indicated by orange and blue colors, respectively) were associated with several, different diseases. Note that up-regulation of GABAAR α3 RNA editing makes an exception as it plays a role in development (indicated by gray text color).

Mentions: In patients with amyotrophic lateral sclerosis, decreased RNA editing at the Q/R site was found to occur in motor neurons (Kwak and Kawahara, 2005; Figure 2). In fact, ADAR2 gene targeting in motor neurons provokes a decline in motor function and the phenotype can be reverted if the mice express RNA edited GluA2 (Higuchi et al., 2000; Hideyama et al., 2010). Reduced A-to-I RNA editing at the Q/R site of GluA2 was furthermore shown to be associated with glioblastoma (Maas et al., 2001; Figure 2). However, in spinal cord injury and glioblastoma, the developmentally increasing pattern of A-to-I RNA editing of many gene transcripts seems to be disrupted (Hwang et al., 2016), raising the question about underlying mechanisms of these diseases (Fu et al., 2016), including investigation of “master” genes that regulate function of down-stream genes and thus govern signaling cascades involved in disease. Regarding GluA2 under-editing, which was more pronounced in glioblastoma compared to neighboring non-tumor tissue (Hwang et al., 2016), and taking into account that brain tumor cells can release glutamate by transferrin-mediated iron accumulation (Chirasani et al., 2009), reduced RNA editing and increased calcium signaling through GluA2 may contribute to aggressiveness of tumor growth and expansion. Regarding spinal cord injury in a mouse model (Chen et al., 2013), decreased RNA editing of GluA2 in the epicenter of the injured site actually points to a disease-promoting mechanism, as cellular calcium overload should promote neurodegeneration.


RNA Editing — Systemic Relevance and Clue to Disease Mechanisms?
Pathophysiological implications of altered ADAR-dependent RNA editing in disease. Both up- and down-regulation of A-to-I RNA editing (indicated by orange and blue colors, respectively) were associated with several, different diseases. Note that up-regulation of GABAAR α3 RNA editing makes an exception as it plays a role in development (indicated by gray text color).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5120146&req=5

Figure 2: Pathophysiological implications of altered ADAR-dependent RNA editing in disease. Both up- and down-regulation of A-to-I RNA editing (indicated by orange and blue colors, respectively) were associated with several, different diseases. Note that up-regulation of GABAAR α3 RNA editing makes an exception as it plays a role in development (indicated by gray text color).
Mentions: In patients with amyotrophic lateral sclerosis, decreased RNA editing at the Q/R site was found to occur in motor neurons (Kwak and Kawahara, 2005; Figure 2). In fact, ADAR2 gene targeting in motor neurons provokes a decline in motor function and the phenotype can be reverted if the mice express RNA edited GluA2 (Higuchi et al., 2000; Hideyama et al., 2010). Reduced A-to-I RNA editing at the Q/R site of GluA2 was furthermore shown to be associated with glioblastoma (Maas et al., 2001; Figure 2). However, in spinal cord injury and glioblastoma, the developmentally increasing pattern of A-to-I RNA editing of many gene transcripts seems to be disrupted (Hwang et al., 2016), raising the question about underlying mechanisms of these diseases (Fu et al., 2016), including investigation of “master” genes that regulate function of down-stream genes and thus govern signaling cascades involved in disease. Regarding GluA2 under-editing, which was more pronounced in glioblastoma compared to neighboring non-tumor tissue (Hwang et al., 2016), and taking into account that brain tumor cells can release glutamate by transferrin-mediated iron accumulation (Chirasani et al., 2009), reduced RNA editing and increased calcium signaling through GluA2 may contribute to aggressiveness of tumor growth and expansion. Regarding spinal cord injury in a mouse model (Chen et al., 2013), decreased RNA editing of GluA2 in the epicenter of the injured site actually points to a disease-promoting mechanism, as cellular calcium overload should promote neurodegeneration.

View Article: PubMed Central - PubMed

ABSTRACT

Recent advances in sequencing technologies led to the identification of a plethora of different genes and several hundreds of amino acid recoding edited positions. Changes in editing rates of some of these positions were associated with diseases such as atherosclerosis, myopathy, epilepsy, major depression disorder, schizophrenia and other mental disorders as well as cancer and brain tumors. This review article summarizes our current knowledge on that front and presents glycine receptor C-to-U RNA editing as a first example of disease-associated increased RNA editing that includes assessment of disease mechanisms of the corresponding gene product in an animal model.

No MeSH data available.