| First Author | Bajad P | Year | 2020 |
| Journal | Nucleic Acids Res | Volume | 48 |
| Issue | 6 | Pages | 3286-3303 |
| PubMed ID | 31956894 | Mgi Jnum | J:292357 |
| Mgi Id | MGI:6435596 | Doi | 10.1093/nar/gkaa025 |
| Citation | Bajad P, et al. (2020) An internal deletion of ADAR rescued by MAVS deficiency leads to a minute phenotype. Nucleic Acids Res 48(6):3286-3303 |
| abstractText | The RNA-editing protein ADAR is essential for early development in the mouse. Genetic evidence suggests that A to I editing marks endogenous RNAs as 'self'. Today, different Adar knockout alleles have been generated that show a common phenotype of apoptosis, liver disintegration, elevated immune response and lethality at E12.5. All the Adar knockout alleles can be rescued by a concomitant deletion of the innate immunity genes Mavs or Ifih1 (MDA5), albeit to different extents. This suggests multiple functions of ADAR. We analyze AdarDelta7-9 mice that show a unique growth defect phenotype when rescued by Mavs. We show that AdarDelta7-9 can form a truncated, unstable, editing deficient protein that is mislocalized. Histological and hematologic analysis of these mice indicate multiple tissue- and hematopoietic defects. Gene expression profiling shows dysregulation of Rps3a1 and Rps3a3 in rescued AdarDelta7-9. Consistently, a distortion in 40S and 60S ribosome ratios is observed in liver cells. This dysregulation is also seen in AdarDelta2-13; Mavs-/- but not in AdarE861A/E861A; Ifih1-/- mice, suggesting editing-independent functions of ADAR in regulating expression levels of Rps3a1 and Rps3a3. In conclusion, our study demonstrates the importance of ADAR in post-natal development which cannot be compensated by ADARB1. |
