Harnessing ADAR-Mediated Site-Specific RNA Editing in Immune-Related Disease: Prediction and Therapeutic Implications

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Jan 11

PMID 38203521

Authors

Shenghui Weng

Xinyi Yang

Nannan Yu

Peng-Cheng Wang

Sidong Xiong

Hang Ruan

Affiliations

Soon will be listed here.

Abstract

ADAR (Adenosine Deaminases Acting on RNA) proteins are a group of enzymes that play a vital role in RNA editing by converting adenosine to inosine in RNAs. This process is a frequent post-transcriptional event observed in metazoan transcripts. Recent studies indicate widespread dysregulation of ADAR-mediated RNA editing across many immune-related diseases, such as human cancer. We comprehensively review ADARs' function as pattern recognizers and their capability to contribute to mediating immune-related pathways. We also highlight the potential role of site-specific RNA editing in maintaining homeostasis and its relationship to various diseases, such as human cancers. More importantly, we summarize the latest cutting-edge computational approaches and data resources for predicting and analyzing RNA editing sites. Lastly, we cover the recent advancement in site-directed ADAR editing tool development. This review presents an up-to-date overview of ADAR-mediated RNA editing, how site-specific RNA editing could potentially impact disease pathology, and how they could be harnessed for therapeutic applications.

Citing Articles

RNA modifications in cancer.

Wu H, Chen S, Li X, Li Y, Shi H, Qing Y MedComm (2020). 2025; 6(1):e70042.

PMID: 39802639 PMC: 11718328. DOI: 10.1002/mco2.70042.

References

Rieder L, Staber C, Hoopengardner B, Reenan R . Tertiary structural elements determine the extent and specificity of messenger RNA editing. Nat Commun. 2013; 4:2232. DOI: 10.1038/ncomms3232. View

Wu S, Fan Z, Kim P, Huang L, Zhou X . The Integrative Studies on the Functional A-to-I RNA Editing Events in Human Cancers. Genomics Proteomics Bioinformatics. 2023; 21(3):619-631. PMC: 10787018. DOI: 10.1016/j.gpb.2022.12.010. View

Hsiao Y, Bahn J, Yang Y, Lin X, Tran S, Yang E . RNA editing in nascent RNA affects pre-mRNA splicing. Genome Res. 2018; 28(6):812-823. PMC: 5991522. DOI: 10.1101/gr.231209.117. View

Li Q, Gloudemans M, Geisinger J, Fan B, Aguet F, Sun T . RNA editing underlies genetic risk of common inflammatory diseases. Nature. 2022; 608(7923):569-577. PMC: 9790998. DOI: 10.1038/s41586-022-05052-x. View

Ramaswami G, Li J . RADAR: a rigorously annotated database of A-to-I RNA editing. Nucleic Acids Res. 2013; 42(Database issue):D109-13. PMC: 3965033. DOI: 10.1093/nar/gkt996. View

Danecek P, Nellaker C, McIntyre R, Buendia-Buendia J, Bumpstead S, Ponting C . High levels of RNA-editing site conservation amongst 15 laboratory mouse strains. Genome Biol. 2012; 13(4):26. PMC: 3446300. DOI: 10.1186/gb-2012-13-4-r26. View

Rieder L, Savva Y, Reyna M, Chang Y, Dorsky J, Rezaei A . Dynamic response of RNA editing to temperature in Drosophila. BMC Biol. 2015; 13:1. PMC: 4299485. DOI: 10.1186/s12915-014-0111-3. View

Piechotta M, Wyler E, Ohler U, Landthaler M, Dieterich C . JACUSA: site-specific identification of RNA editing events from replicate sequencing data. BMC Bioinformatics. 2017; 18(1):7. PMC: 5210316. DOI: 10.1186/s12859-016-1432-8. View

Hosaka T, Yamashita T, Teramoto S, Hirose N, Tamaoka A, Kwak S . ADAR2-dependent A-to-I RNA editing in the extracellular linear and circular RNAs. Neurosci Res. 2018; 147:48-57. DOI: 10.1016/j.neures.2018.11.005. View

10.

Teoh P, An O, Chung T, Chooi J, Toh S, Fan S . Aberrant hyperediting of the myeloma transcriptome by ADAR1 confers oncogenicity and is a marker of poor prognosis. Blood. 2018; 132(12):1304-1317. DOI: 10.1182/blood-2018-02-832576. View

11.

Herzner A, Khan Z, Van Nostrand E, Chan S, Cuellar T, Chen R . ADAR and hnRNPC deficiency synergize in activating endogenous dsRNA-induced type I IFN responses. J Exp Med. 2021; 218(9). PMC: 8313407. DOI: 10.1084/jem.20201833. View

12.

Yang W, Chendrimada T, Wang Q, Higuchi M, Seeburg P, Shiekhattar R . Modulation of microRNA processing and expression through RNA editing by ADAR deaminases. Nat Struct Mol Biol. 2005; 13(1):13-21. PMC: 2950615. DOI: 10.1038/nsmb1041. View

13.

Lehmann K, Bass B . Double-stranded RNA adenosine deaminases ADAR1 and ADAR2 have overlapping specificities. Biochemistry. 2000; 39(42):12875-84. DOI: 10.1021/bi001383g. View

14.

Chen T, Xiang J, Zhu S, Chen S, Yin Q, Zhang X . ADAR1 is required for differentiation and neural induction by regulating microRNA processing in a catalytically independent manner. Cell Res. 2015; 25(4):459-76. PMC: 4387555. DOI: 10.1038/cr.2015.24. View

15.

Kawahara Y, Zinshteyn B, Chendrimada T, Shiekhattar R, Nishikura K . RNA editing of the microRNA-151 precursor blocks cleavage by the Dicer-TRBP complex. EMBO Rep. 2007; 8(8):763-9. PMC: 1978079. DOI: 10.1038/sj.embor.7401011. View

16.

Sommer B, Kohler M, Sprengel R, Seeburg P . RNA editing in brain controls a determinant of ion flow in glutamate-gated channels. Cell. 1991; 67(1):11-9. DOI: 10.1016/0092-8674(91)90568-j. View

17.

Ward S, George C, Welch M, Liou L, Hahm B, Lewicki H . RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis. Proc Natl Acad Sci U S A. 2010; 108(1):331-6. PMC: 3017198. DOI: 10.1073/pnas.1017241108. View

18.

Sinigaglia K, Wiatrek D, Khan A, Michalik D, Sambrani N, Sedmik J . ADAR RNA editing in innate immune response phasing, in circadian clocks and in sleep. Biochim Biophys Acta Gene Regul Mech. 2018; 1862(3):356-369. DOI: 10.1016/j.bbagrm.2018.10.011. View

19.

Wang Y, Xu X, Yu S, Jeong K, Zhou Z, Han L . Systematic characterization of A-to-I RNA editing hotspots in microRNAs across human cancers. Genome Res. 2017; 27(7):1112-1125. PMC: 5495064. DOI: 10.1101/gr.219741.116. View

20.

Lv D, Xu K, Yang C, Liu Y, Luo Y, Zhou W . PRES: a webserver for decoding the functional perturbations of RNA editing sites. Brief Bioinform. 2022; 23(4). DOI: 10.1093/bib/bbac242. View