Processes 2018, 6,42
Author Contributions: J.T.R. and G.M.B. conceived and designed the experiments; J.T.R., D.G.P., V.M.K., S.V.A.,
C.J.P., D.H., A.C., E.C.B., M.M.M. performed the experiments; J.T.R., V.M.K., and G.M.B. analyzed the data; T.D.S.
and G.M.B. contributed reagents/materials/analysis tools; J.T.R., D.G.P., V.M.K., S.V.A., C.J.P., D.H., A.C., E.C.B.,
M.M., T.D.S. and G.M.B. wrote/edited the paper.
Funding: Funding was provided in part by NSF CAREER grant 1350064 (G.M.B.) awarded by Division of
Molecular and Cellular Biosciences (with co-funding from NSF EPSCoR) and in part by the Abraham A. Mitchell
Cancer Research Fund (G.M.B.). Graduate funding was provided in part by Alabama Commission on Higher
Education ALEPSCoR grants 150380 (J.T.R.), 160330 (V.M.K.), 170232 (V.M.K.) and 170233 (D.H.).
Acknowledgments: We thank the University of South Alabama College of Arts and Sciences, College of Medicine
and the Mitchell Cancer Institute for ongoing support.
Conflicts of Interest: The authors declare no conflict of interest.
References
1.
Bazak, L.; Haviv, A.; Barak, M.; Jacob-Hirsch, J.; Deng, P.; Zhang, R.; Levanon, E.Y. A-to-I RNA editing
occurs at over a hundred million genomic sites, located in a majority of human genes. Genome Res. 2014,
24, 365–376. [CrossRef][PubMed]
2.
Peng, Z.; Cheng, Y.; Tan, B.C.; Kang, L.; Tian, Z.; Zhu, Y.; Guo, J. Comprehensive analysis of RNA-Seq data
reveals extensive RNA editing in a human transcriptome. Nat. Biotechnol. 2012, 30, 253–260. [CrossRef]
[PubMed]
3.
Li, J.B. Genome-wide identification of human RNA editing sites by parallel DNA capturing and sequencing.
Science 2009, 324, 1210–1213. [CrossRef][PubMed]
4.
Park, E.; Williams, B.; Wold, B.J.; Mortazavi, A. RNA editing in the human ENCODE RNA-seq data.
Genome Res. 2012, 22, 1626–1633. [CrossRef][PubMed]
5.
Bahn, J.H. Accurate identification of A-to-I RNA editing in human by transcriptome sequencing. Genome Res.
2012, 22, 142–150. [CrossRef][PubMed]
6.
Maas, S. Genome-wide evaluation and discovery of vertebrate A-to-I RNA editing sites. Biochem. Biophys.
Res. Commun. 2011, 412, 407–412. [CrossRef][PubMed]
7.
Nishikura, K. Functions and regulation of RNA editing by ADAR deaminases. Annu. Rev. Biochem. 2010,
79, 321–349. [CrossRef][PubMed]
8.
Chen, L.L.; Carmichael, G.G. Gene regulation by SINES and inosines: Biological consequences of A-to-I
editing of Alu element inverted repeats. Cell Cycle 2008, 7, 3294–3301. [CrossRef][PubMed]
9.
Athanasiadis, A.; Rich, A.; Maas, S. Widespread A-to-I RNA editing of Alu-containing mRNAs in the human
transcriptome. PLoS Biol. 2004, 2, e391. [CrossRef][PubMed]
10. Kim, D.D.; Kim, T.T.; Walsh, T.; Kobayashi, Y.; Matise, T.C.; Buyske, S.; Gabriel, A. Widespread RNA editing
of embedded alu elements in the human transcriptome. Genome Res. 2004, 14, 1719–1725. [CrossRef]
[PubMed]
11. Seeburg, P.H. A-to-I editing: New and old sites, functions and speculations. Neuron 2002, 35, 17–20.
[CrossRef]
12. Rieder, L.E.; Reenan, R.A. The intricate relationship between RNA structure, editing, and splicing. Semin. Cell
Dev. Biol. 2012, 23, 281–288. [CrossRef][PubMed]
13. Qin, Y.R.; Qiao, J.J.; Chan, T.H.; Zhu, Y.H.; Li, F.F.; Liu, H.; Chen, L. Adenosine-to-inosine RNA editing
mediated by ADARs in esophageal squamous cell carcinoma. Cancer Res. 2014, 74, 840–851. [CrossRef]
[PubMed]
14. Jiang, Q.; Crews, L.A.; Barrett, C.L.; Chun, H.J.; Court, A.C.; Isquith, J.M.; Zipeto, M.A.; Dao, K.H.T. ADAR1
promotes malignant progenitor reprogramming in chronic myeloid leukemia. Proc. Natl. Acad. Sci. USA
2013, 110, 1041–1046. [CrossRef][PubMed]
15. Chen, L.; Li, Y.; Lin, C.H.; Chan, T.H.; Chow, R.K.; Song, Y.; Qi, L. Recoding RNA editing of AZIN1
predisposes to hepatocellular carcinoma. Nat. Med. 2013, 19, 209–216. [CrossRef][PubMed]
16. Steinman, R.A. Deletion of the RNA-editing enzyme ADAR1 causes regression of established chronic
myelogenous leukemia in mice. Int. J. Cancer 2013, 132, 1741–1750. [CrossRef][PubMed]
17. Choudhury, Y. Attenuated adenosine-to-inosine editing of microRNA-376a* promotes invasiveness of
glioblastoma cells. J. Clin. Investig. 2012, 122, 4059–4076. [CrossRef][PubMed]
141
Author Contributions: J.T.R. and G.M.B. conceived and designed the experiments; J.T.R., D.G.P., V.M.K., S.V.A.,
C.J.P., D.H., A.C., E.C.B., M.M.M. performed the experiments; J.T.R., V.M.K., and G.M.B. analyzed the data; T.D.S.
and G.M.B. contributed reagents/materials/analysis tools; J.T.R., D.G.P., V.M.K., S.V.A., C.J.P., D.H., A.C., E.C.B.,
M.M., T.D.S. and G.M.B. wrote/edited the paper.
Funding: Funding was provided in part by NSF CAREER grant 1350064 (G.M.B.) awarded by Division of
Molecular and Cellular Biosciences (with co-funding from NSF EPSCoR) and in part by the Abraham A. Mitchell
Cancer Research Fund (G.M.B.). Graduate funding was provided in part by Alabama Commission on Higher
Education ALEPSCoR grants 150380 (J.T.R.), 160330 (V.M.K.), 170232 (V.M.K.) and 170233 (D.H.).
Acknowledgments: We thank the University of South Alabama College of Arts and Sciences, College of Medicine
and the Mitchell Cancer Institute for ongoing support.
Conflicts of Interest: The authors declare no conflict of interest.
References
1.
Bazak, L.; Haviv, A.; Barak, M.; Jacob-Hirsch, J.; Deng, P.; Zhang, R.; Levanon, E.Y. A-to-I RNA editing
occurs at over a hundred million genomic sites, located in a majority of human genes. Genome Res. 2014,
24, 365–376. [CrossRef][PubMed]
2.
Peng, Z.; Cheng, Y.; Tan, B.C.; Kang, L.; Tian, Z.; Zhu, Y.; Guo, J. Comprehensive analysis of RNA-Seq data
reveals extensive RNA editing in a human transcriptome. Nat. Biotechnol. 2012, 30, 253–260. [CrossRef]
[PubMed]
3.
Li, J.B. Genome-wide identification of human RNA editing sites by parallel DNA capturing and sequencing.
Science 2009, 324, 1210–1213. [CrossRef][PubMed]
4.
Park, E.; Williams, B.; Wold, B.J.; Mortazavi, A. RNA editing in the human ENCODE RNA-seq data.
Genome Res. 2012, 22, 1626–1633. [CrossRef][PubMed]
5.
Bahn, J.H. Accurate identification of A-to-I RNA editing in human by transcriptome sequencing. Genome Res.
2012, 22, 142–150. [CrossRef][PubMed]
6.
Maas, S. Genome-wide evaluation and discovery of vertebrate A-to-I RNA editing sites. Biochem. Biophys.
Res. Commun. 2011, 412, 407–412. [CrossRef][PubMed]
7.
Nishikura, K. Functions and regulation of RNA editing by ADAR deaminases. Annu. Rev. Biochem. 2010,
79, 321–349. [CrossRef][PubMed]
8.
Chen, L.L.; Carmichael, G.G. Gene regulation by SINES and inosines: Biological consequences of A-to-I
editing of Alu element inverted repeats. Cell Cycle 2008, 7, 3294–3301. [CrossRef][PubMed]
9.
Athanasiadis, A.; Rich, A.; Maas, S. Widespread A-to-I RNA editing of Alu-containing mRNAs in the human
transcriptome. PLoS Biol. 2004, 2, e391. [CrossRef][PubMed]
10. Kim, D.D.; Kim, T.T.; Walsh, T.; Kobayashi, Y.; Matise, T.C.; Buyske, S.; Gabriel, A. Widespread RNA editing
of embedded alu elements in the human transcriptome. Genome Res. 2004, 14, 1719–1725. [CrossRef]
[PubMed]
11. Seeburg, P.H. A-to-I editing: New and old sites, functions and speculations. Neuron 2002, 35, 17–20.
[CrossRef]
12. Rieder, L.E.; Reenan, R.A. The intricate relationship between RNA structure, editing, and splicing. Semin. Cell
Dev. Biol. 2012, 23, 281–288. [CrossRef][PubMed]
13. Qin, Y.R.; Qiao, J.J.; Chan, T.H.; Zhu, Y.H.; Li, F.F.; Liu, H.; Chen, L. Adenosine-to-inosine RNA editing
mediated by ADARs in esophageal squamous cell carcinoma. Cancer Res. 2014, 74, 840–851. [CrossRef]
[PubMed]
14. Jiang, Q.; Crews, L.A.; Barrett, C.L.; Chun, H.J.; Court, A.C.; Isquith, J.M.; Zipeto, M.A.; Dao, K.H.T. ADAR1
promotes malignant progenitor reprogramming in chronic myeloid leukemia. Proc. Natl. Acad. Sci. USA
2013, 110, 1041–1046. [CrossRef][PubMed]
15. Chen, L.; Li, Y.; Lin, C.H.; Chan, T.H.; Chow, R.K.; Song, Y.; Qi, L. Recoding RNA editing of AZIN1
predisposes to hepatocellular carcinoma. Nat. Med. 2013, 19, 209–216. [CrossRef][PubMed]
16. Steinman, R.A. Deletion of the RNA-editing enzyme ADAR1 causes regression of established chronic
myelogenous leukemia in mice. Int. J. Cancer 2013, 132, 1741–1750. [CrossRef][PubMed]
17. Choudhury, Y. Attenuated adenosine-to-inosine editing of microRNA-376a* promotes invasiveness of
glioblastoma cells. J. Clin. Investig. 2012, 122, 4059–4076. [CrossRef][PubMed]
141