Table 1 Key studies: A-to-I RNA editing and human disease

Amyotrophic lateral sclerosis (ALS)

Downregulation of ADAR2 expression and GluA2 editing in ALS

Human patients

[20, 21]

Conditional ADAR2 knockout produces ALS-like symptoms that are rescued by edited GluA2

In vivo, mice

[23]

Unedited GluA2 causes mislocation of TDP-43 also observed in sporadic ALS

In vivo, mice

[24]

In vitro, mouse cells

In vitro, human cells

Astrocytoma

Correlation between ADAR2 activity and malignancy

Pediatric astrocytoma tissue

[28]

In vitro, human cells

Constant expression of ADAR2 but upregulation of ADAR1

Overexpression of ADAR2 results in decreased proliferation and mobility

Influx of Ca²⁺ results in an activation of the Akt pathway, which is rescued by edited GluA2

In vitro, human cells

[29]

ADAR2 edits CDC14B mRNA, promoting its translation. This leads to degradation of Skp2, which upregulates p21 and p27. This prevents S-phase transition and tumor growth

Mouse xenograft

[30]

Aicardi-Goutières syndrome (AGS)

Novel Adar1 mutations associated with AGS

Human patients

[53]

Hepatocellular carcinoma (HCC)

ADAR1 activity correlated with tumor aggressiveness ADAR1 edits AZIN1, which increases its inhibition of antizyme

Human tumor specimens

[62]

Mouse xenograft

In vitro, human cells

This upregulates ODC and CCND1, increasing proliferation and mobility

Computational model

Measles virus

Biased hypermutation in matrix gene

Human patients

[71]

Hypermutation promotes viral infection

In vivo, mouse

[73]

In vitro, mouse cells

ADAR1 promotes viral infection

In vitro, human cells

[74]

Metastatic melanoma

Cancer amplifies genes encoding microRNAs that target ADAR1

Mouse xenograft

[60]

In vitro, human cells

This interferes with the regulation of >100 microRNAs and promotes tumorigenicity