The double-stranded RNA-specific adenosine deaminase enzyme family are encoded by the ADAR family genes.[5] ADAR stands for adenosine deaminase acting on RNA.[6][7] This article focuses on the ADAR proteins; This article details the evolutionary history, structure, function, mechanisms and importance of all proteins within this family.[5]
ADAR enzymes bind to double-stranded RNA (dsRNA) and convert adenosine to inosine (hypoxanthine) by deamination.[8] ADAR proteins act post-transcriptionally, changing the nucleotide content of RNA.[9] The conversion from adenosine to inosine (A to I) in the RNA disrupts the normal A:U pairing, destabilizing the RNA. Inosine is structurally similar to guanine (G) which leads to inosine to cytosine (I:C) binding.[10] Inosine typically mimics guanosine during translation but can also bind to uracil, cytosine, and adenosine, though it is not favored.
Codon changes may arise from RNA editing leading to changes in the coding sequences for proteins and their functions.[11] Most editing sites are found in noncoding regions of RNA such as untranslated regions (UTRs), Alu elements, and long interspersed nuclear elements (LINEs).[12] Codon changes can give rise to alternate transcriptional splice variants. ADAR impacts the transcriptome in editing-independent ways, likely by interfering with other RNA-binding proteins.[9]
Mutations in this gene are associated with several diseases including HIV, measles, and melanoma. Recent research supports a linkage between RNA-editing and nervous system disorders such as amyotrophic lateral sclerosis (ALS). Atypical RNA editing linked to ADAR may also correlate to mental disorders such as schizophrenia, epilepsy, and suicidal depression.[13]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000160710 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027951 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b Savva YA, Rieder LE, Reenan RA (December 2012). "The ADAR protein family". Genome Biology. 13 (12): 252. doi:10.1186/gb-2012-13-12-252. PMC 3580408. PMID 23273215.
- ^ "Entrez Gene: ADAR Adenosine Deaminase Acting on RNA".
- ^ Kim U, Wang Y, Sanford T, Zeng Y, Nishikura K (November 1994). "Molecular cloning of cDNA for double-stranded RNA adenosine deaminase, a candidate enzyme for nuclear RNA editing". Proceedings of the National Academy of Sciences of the United States of America. 91 (24): 11457–11461. Bibcode:1994PNAS...9111457K. doi:10.1073/pnas.91.24.11457. PMC 45250. PMID 7972084.
- ^ Samuel CE (2012). Adenosine deaminases acting on RNA (ADARs) and A-to-I editing. Heidelberg: Springer. ISBN 978-3-642-22800-1.
- ^ a b "ADAR". NCBI. U.S. National Library of Medicine.
- ^ Licht K, Hartl M, Amman F, Anrather D, Janisiw MP, Jantsch MF (January 2019). "Inosine induces context-dependent recoding and translational stalling". Nucleic Acids Research. 47 (1): 3–14. doi:10.1093/nar/gky1163. PMC 6326813. PMID 30462291.
- ^ Nishikura K (7 June 2010). "Functions and regulation of RNA editing by ADAR deaminases". Annual Review of Biochemistry. 79 (1): 321–349. doi:10.1146/annurev-biochem-060208-105251. PMC 2953425. PMID 20192758.
- ^ Tajaddod M, Jantsch MF, Licht K (March 2016). "The dynamic epitranscriptome: A to I editing modulates genetic information". Chromosoma. 125 (1): 51–63. doi:10.1007/s00412-015-0526-9. PMC 4761006. PMID 26148686.
- ^ Savva YA, Rieder LE, Reenan RA (December 2012). "The ADAR protein family". Genome Biology. 13 (12): 252. doi:10.1186/gb-2012-13-12-252. PMC 3580408. PMID 23273215.