Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5644_Библиотеки_им_академика_М_И_Перельмана
.pdf
12.4 Concluding Remarks 335
https://t.me/med1917
Overexpression of the methyltransferase brillarin results in increased levels of
2′-O-Me modications, decreased translational quality control, and increased internal ribosome entry site (IRES)-mediated translation of cancer-related genes [295].
Ribosome biogenesis has become an attractive anti-cancer target, and multiple
compounds exist that inhibit rRNA transcription, processing, or ribosome assembly
[296]. These drugs include platinum-based compounds, the RNA polymerase I
inhibitor actinomycin D, 5-uorouridine, and poly-ADP ribose polymerase (PARP)
inhibitors. A newer promising drug, CX-5461 [297], has been shown to inhibit
Pol I transcription and has already completed a phase 1 clinical trial. To the
best of our knowledge, no treatments are yet in development that target specic
rRNA-modifying enzymes or snoRNP levels; however, such compounds could
conceivably be added to the arsenal of ribosome biogenesis inhibitors.
12.4 Concluding Remarks
The study of RNA modications has emerged as a major area in biomedical research.
As highlighted in this chapter, there is a large diversity of post-transcriptional modications occurring on all types of RNA. These modications regulate gene expression through dierent mechanisms and playan important role in biology.Clear links
to human disease resulting from absence or dysregulation of modications have
been established, and therapeutics targeting RNA modication-associated proteins,
or exploiting modication pathways, are in active development. Arguably, we have
only scratched the surface of the ∼170 dierent modied nucleotides that are known
in biological systems.
With expanding studies of RNA modication biology and disease-associated
phenotypes, we urge caution in interpreting the eects of modication pathways
given the signicant gaps in the characterization of RNA modication sites and
associated molecular mechanisms. RNA modication mapping is still largely a
cottage industry [252], and we lack unied approaches for characterizing the
distribution and stoichiometry of multiple RNA modications transcriptome-wide
in a single biological sample. Recently, direct RNA sequencing technologies such
as nanopore sequencing (commercialized by Oxford Nanopore Technologies) oer
the promise of quantitative modication sequencing across multiple modication
types [253]; however, it is becoming apparent that only a subset of epitranscriptomic modications can be readily detected using this technology in its current
implementation [298]. In addition to modication mapping, identication and
characterization of relevant RNA-modifying enzymes is still incomplete in many
organisms. Continued innovation in technologies for mapping RNA modications
[167, 299] and identifying and characterizing RNA-modifying enzymes [65, 300]
are likely to have a considerable impact on the future of the epitranscriptomics
eld. Once these methods are in place and widely accessible, functional studies of
individual modication sites, connecting observations in dened in vitro systems
with cell biological and organismal phenotypes, should enable the development of
rigorous molecular frameworks for understanding RNA modication biology.
336 12 Drugging the Epitranscriptome
https://t.me/med1917
Finally, despite the rapid development of METTL3 inhibitors, there are currently few available small-molecule modulators of RNA-modifying enzymes.
While nucleic-acid-modifying enzymes do present some unique molecular
challenges compared to more traditional protein targets, the success with
METTL3 and the recent emergence of ADAR1 inhibitors suggest that the
standard tools of small-molecule discovery and medicinal chemistry can be
readily applied to this class of proteins. Therefore, leveraging advances in
chemical biology, structural biology, medicinal chemistry, and in silico screening, among other approaches, will likely yield promising starting points for
small-molecule probes. Such compounds will not only accelerate therapeutic
development but can also serve as tool compounds to facilitate the chemical
genetic exploration of the diverse biological role(s) of RNA modication-associated
proteins.
References
1 Cohn, W.E. and Volkin, E. (1951). Nucleoside-5′-phosphates from ribonucleic
acid. Nature 167: 483–484.
2 de Crécy-Lagard, V. and Jaroch, M. (2021). Functions of bacterial tRNA modi-
cations:
3 de Crecy-Lagard, V. , Boccaletto, P., Mangleburg, C.G. et al. (2019). Matching
tRNA modications in humans to their known and predicted enzymes. Nucleic
Acids Res. 47: 2143–2159.
4 Jia, G., Fu, Y.E., Zhao, X.U. et al. (2011). N6-Methyladenosine in nuclear RNA
is a major substrate of the obesity-associated FTO. Nat. Chem. Biol. 7: 885–887.
5 Zheng, G., Dahl, J.A., Niu, Y. et al. (2013). ALKBH5 is a mammalian RNA
demethylase that impacts RNA metabolism and mouse fertility. Mol. Cell 49:
18–29.
6 Jia, G., Yang, C.G., Yang, S. et al. (2008). Oxidative demethylation of
3-methylthymine and 3-methyluracil in single-stranded DNA and RNA by
mouse and human FTO. FEBS Lett. 582: 3313–3319.
7 Dominissini, D. et al. (2016). The dynamic N(1)-methyladenosine methylome in
eukaryotic messenger RNA. Nature 530: 441–446.
8 Li, X., Xiong, X., Wang, K. et al. (2016). Transcriptome-wide mapping reveals
reversible and dynamic N(1)-methyladenosine methylome. Nat. Chem. Biol. 12:
311–316.
9 Roundtree, I.A., Evans, M.E., Pan, T., and He, C. (2017). Dynamic RNA modi-
cations
10 Liu, F., Clark, W. , Luo, G. et al. (2016). ALKBH1-mediated tRNA demethylation
regulates translation. Cell 167: 816–828.e816.
11 Suzuki, T. (2021). The expanding world of tRNA modications and their dis-
ease relevance. Nat. Rev. Mol. Cell Biol. 22: 375–392.
12 Yang, C., Hu, Y., Zhou, B. et al. (2020). The role of m6A modication in physi-
ology and disease. Cell Death Dis. 11: 960.
from ubiquity to diversity. Trends Microbiol. 29: 41–53.
in gene expression regulation. Cell 169: 1187–1200.
References 337
https://t.me/med1917
13 Chujo, T. and Tomizawa, K. (2021). Human transfer RNA modopathies: dis-
eases caused by aberrations in transfer RNA modications. FEBS J. 288:
7096–7122.
14 Nombela, P., Miguel-López, B., and Blanco, S. (2021). The role of m6A, m5C
and Ψ RNA modications in cancer: novel therapeutic opportunities. Mol.
Cancer 20: 18.
15 Konno, M. and Ishii, H. (2021). Epitranscriptomics (ed. S. Jurga and J.
Barciszewski), 121–140. Cham: Springer International Publishing.
16 Cui, L., Ma, R., Cai, J. et al. (2022). RNA modications: importance in immune
cell biology and related diseases. Signal Transduction Targeted Ther. 7: 334.
17 Pereira, M., Francisco, S., Varanda, A.S. et al. (2018). Impact of tRNA modica-
tions and tRNA-modifying enzymes on proteostasis and human disease. Int. J.
Mol. Sci. 19: 3738.
18 Torres, A.G., Batlle, E., and Ribas de Pouplana, L. (2014). Role of tRNA modi-
in human diseases. Trends Mol. Med. 20: 306–314.
cations
19 Sarin, L.P. and Leidel, S.A. (2014). Modify or die? – RNA modication defects
in metazoans. RNA Biol. 11: 1555–1567.
20 Jonkhout, N., Tran, J., Smith, M.A. et al. (2017). The RNA modication land-
scape in human disease. RNA 23: 1754–1769.
21 Boccaletto, P., Stefaniak, F., Ray, A. et al. (2021). MODOMICS: a database of
RNA modication pathways. 2021 update. Nucleic Acids Res. 50: D231–D235.
22 Höfer, K. and Jäschke, A. (2018). Epitranscriptomics: RNA modications
in bacteria and archaea. Microbiol. Spectrum 6, https://doi.org/10.1128/
microbiolspec.rwr-0015-2017.
23 Arguello, A.E., DeLiberto, A.N., and Kleiner, R.E. (2017). RNA chemical
proteomics reveals the N6-methyladenosine (m6A)-regulated protein–RNA
interactome. JACS 139: 17249–17252.
24 Yang, X., Yang, Y., Sun, B.F. et al. (2017). 5-methylcytosine promotes mRNA
export — NSUN2 as the methyltransferase and ALYREF as an m5C reader. Cell
Res. 27: 606–625.
25 Roundtree, I.A., Luo, G.Z., Zhang, Z. et al. (2017). YTHDC1 mediates nuclear
export of N6-methyladenosine methylated mRNAs. eLife 6: e31311.
26 Wang, X., Lu, Z., Gomez, A. et al. (2014). N6-methyladenosine-dependent regu-
lation of messenger RNA stability. Nature 505: 117–120.
27 Shi, H., Wang, X., Lu, Z. et al. (2017). YTHDF3 facilitates translation and decay
of N6-methyladenosine-modied RNA. Cell Res. 27: 315–328.
28 Xiao, W., Adhikari, S., Dahal, U. et al. (2016). Nuclear m6A reader YTHDC1
regulates mRNA splicing. Mol. Cell 61: 507–519.
29 Fu, Y. and Zhuang, X. (2020). m(6)A-binding YTHDF proteins promote stress
granule formation. Nat. Chem. Biol. 16: 955–963.
30 Meyer, K.D., Patil, D.P., Zhou, J. et al. (2015). 5′UTR m6A promotes
cap-independent translation. Cell 163: 999–1010.
31 Mao, Y., Dong, L., Liu, X.M. et al. (2019). m6A in mRNA coding regions pro-
motes translation via the RNA helicase-containing YTHDC2. Nat. Commun. 10:
5332.
338 12 Drugging the Epitranscriptome
https://t.me/med1917
32 Li, A., Chen, Y.S., Ping, X.L. et al. (2017). Cytoplasmic m6A reader YTHDF3
promotes mRNA translation. Cell Res. 27: 444–447.
33 Wang, X., Zhao, B.S., Roundtree, I.A. et al. (2015). N6-methyladenosine modu-
lates messenger RNA translation eciency. Cell 161: 1388–1399.
34 Frye, M., Harada, B.T., Behm, M., and He, C. (2018). RNA modications modu-
late gene expression during development. Science 361: 1346–1349.
35 Wang, Y., Li, Y. , Toth, J.I. et al. (2014). N 6-methyladenosine modication
destabilizes developmental regulators in embryonic stem cells. Nat. Cell Biol.
16: 191–198.
36 Liu, J., Huang, T., Chen, W. et al. (2022). Developmental mRNA m5C landscape
and regulatory innovations of massive m5C modication of maternal mRNAs in
animals. Nat. Commun. 13: 2484.
37 Shi, H., Zhang, X., Weng, Y.L. et al. (2018). m6A facilitates
hippocampus-dependent learning and memory through YTHDF1. Nature 563:
249–253.
38 Karikó, K., Buckstein, M., Ni, H., and Weissman, D. (2005). Suppression of
RNA recognition by toll-like receptors: the impact of nucleoside modication
and the evolutionary origin of RNA. Immunity 23: 165–175.
39 Fakruddin, M., Wei, F.Y., Suzuki, T. et al. (2018). Defective mitochondrial tRNA
taurine modication activates global proteostress and leads to mitochondrial
disease. Cell Rep. 22: 482–496.
40 Ghezzi, D. et al. (2012). Mutations of the mitochondrial-tRNA modier MTO1
cause hypertrophic cardiomyopathy and lactic acidosis. Am. J. Hum. Genet. 90:
1079–1087.
41 Kazuhito, T. and Wei, F.-Y. (2020). Posttranscriptional modications in mito-
chondrial tRNA and its implication in mitochondrial translation and disease. J.
Biochem. 168: 435–444.
42 Kirino, Y., Yasukawa, T., Ohta, S. et al. (2004). Codon-specic translational
defect caused by a wobble modication deciency in mutant tRNA from a
human mitochondrial disease. PNAS 101: 15070–15075.
43 Annapoorna, P.K., Iyer, H., Parnaik, T. et al. (2019). FTO: an emerging molecu-
lar player in neuropsychiatric diseases. Neuroscience 418: 15–24.
44 Bento-Abreu, A., Jager, G., Swinnen, B. et al. (2018). Elongator subunit
3 (ELP3) modies ALS through tRNA modication. Hum. Mol. Genet. 27:
1276–1289.
45 Blanco, S., Dietmann, S., Flores, J.V. et al. (2014). Aberrant methylation of
tRNAs links cellular stress to neuro-developmental disorders. Embo J. 33:
2020–2039.
46 Martinez, F.J., Lee, J.H., Lee, J.E. et al. (2012). Whole exome sequencing iden-
ties a splicing mutation in NSUN2 as a cause of a Dubowitz-like syndrome. J.
Med. Genet. 49: 380–385.
47 Ramos, J. and Fu, D. (2019). The emerging impact of tRNA modications
in the brain and nervous system. Biochim. Biophys. Acta, Gene Regul. 1862:
412–428.
References 339
https://t.me/med1917
48 Barbieri, I. and Kouzarides, T. (2020). Role of RNA modications in cancer.
Nat. Rev. Cancer 20: 303–322.
49 Christo, T. and Zaravinos, A. (2019). RNA editing in the forefront of epitran-
scriptomics and human health. J. Transl. Med. 17: 319.
50 Leptidis, S., Papakonstantinou, E., Diakou, K.I. et al. (2022). Epitranscriptomics
of cardiovascular diseases (review). Int. J. Mol. Med. 49: 9.
51 Qin, Y., Li, L., Luo, E. et al. (2020). Role of m6A RNA methylation in cardiovas-
cular disease (review). Int. J. Mol. Med. 46: 1958–1972.
52 Shak, A.M., Allen, E.G., and Jin, P. (2020). Dynamic N6-methyladenosine RNA
methylation in brain and diseases. Epigenomics 12: 371–380.
53 Song, H., Zhang, J., Liu, B. et al. (2022). Biological roles of RNA m(5)C mod-
ication and its implications in cancer immunotherapy. Biomarker Res. 10:
15.
54 Wang, T., Kong, S., Tao, M., and Ju, S. (2020). The potential role of RNA
N6-methyladenosine in Cancer progression. Mol. Cancer 19: 88.
55 Yen, Y.P. and Chen, J.A. (2021). The m(6)A epitranscriptome on neural develop-
ment and degeneration. J. Biomed. Sci. 28: 40.
56 Zhang, Y., Geng, X., Li, Q. et al. (2020). m6A modication in RNA: biogenesis,
functions and roles in gliomas. J. Exp. Clin. Cancer Res. 39: 192.
57 Trixl, L. and Lusser, A. (2019). The dynamic RNA modication
5-methylcytosine and its emerging role as an epitranscriptomic mark. Wiley
Interdiscip. Rev.: RNA 10: e1510.
58 Kumar, S. and Mohapatra, T. (2021). Deciphering epitranscriptome: modi-
cation of mRNA bases provides a new perspective for post-transcriptional
regulation of gene expression. Front. Cell Dev. Biol. 9.
59 Boo, S.H. and Kim, Y.K. (2020). The emerging role of RNA modications in the
regulation of mRNA stability. Exp. Mol. Med. 52: 400–408.
60 Dominissini, D., Moshitch-Moshkovitz, S., Schwartz, S. et al. (2012). Topology
of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature
485: 201–206.
61 Dominissini, D., Moshitch-Moshkovitz, S., Salmon-Divon, M. et al. (2013).
Transcriptome-wide mapping of N6-methyladenosine by m6A-seq based on
immunocapturing and massively parallel sequencing. Nat. Protoc. 8: 176–189.
62 Schwartz, S., Bernstein, D.A., Mumbach, M.R. et al. (2014). Transcriptome-wide
mapping reveals widespread dynamic-regulated pseudouridylation of ncRNA
and mRNA. Cell 159: 148–162.
63 Carlile, T.M., Rojas-Duran, M.F., Zinshteyn, B. et al. (2014). Pseudouridine
proling reveals regulated mRNA pseudouridylation in yeast and human cells.
Nature 515: 143–146.
64 Paul, M.S. and Bass, B.L. (1998). Inosine exists in mRNA at tissue-specic
levels and is most abundant in brain mRNA. Embo J. 17: 1120–1127.
65 Arguello, A.E., Li, A., Sun, X. et al. (2022). Reactivity-dependent proling of
RNA 5-methylcytidine dioxygenases. Nat. Commun. 13: 4176.
66 Colgan, D.F. and Manley, J.L. (1997). Mechanism and regulation of mRNA
polyadenylation. Genes Dev. 11: 2755–2766.
340 12 Drugging the Epitranscriptome
https://t.me/med1917
67 Di Giammartino, D.C., Nishida, K., and Manley, J.L. (2011). Mechanisms and
consequences of alternative polyadenylation. Mol. Cell 43: 853–866.
68 Galloway, A. and Cowling, V.H. (2019). mRNA cap regulation in mammalian
cell function and fate. Biochim. Biophys. Acta, Gene Regul. Mech. 1862: 270–279.
69 Ramanathan, A., Robb, G.B., and Chan, S.H. (2016). mRNA capping: biological
functions and applications. Nucleic Acids Res. 44: 7511–7526.
70 Rogalska, M.E., Vivori, C., and Valcárcel, J. (2023). Regulation of pre-mRNA
splicing: roles in physiology and disease, and therapeutic prospects. Nat. Rev.
Genet. 24: 251–269.
71 Perry, R.P. and Kelley, D.E. (1974). Existence of methylated messenger RNA in
mouse L cells. Cell 1: 37–42.
72 Desrosiers, R., Friderici, K., and Rottman, F. (1974). Identication of methy-
lated nucleosides in messenger RNA from Noviko hepatoma cells. Proc. Natl.
Acad. Sci. 71: 3971–3975.
73 Meyer, K.D., Saletore, Y., Zumbo, P. et al. (2012). Comprehensive analysis of
mRNA methylation reveals enrichment in 3’ UTRs and near stop codons. Cell
149: 1635–1646.
74 Meyer, K.D. (2019). DART-seq: an antibody-free method for global m(6)A detec-
tion. Nat. Methods 16: 1275–1280.
75 Zhang, Z., Chen, L.Q., Zhao, Y.L. et al. (2019). Single-base mapping of m6Aby
an antibody-independent method. Sci. Adv. 5: eaax0250.
76 Garcia-Campos, M.A., Edelheit, S., Toth, U. et al. (2019). Deciphering the “m6A
code” via antibody-independent quantitative proling. Cell 178: 731–747. e716.
77 Chen, K., Lu, Z., Wang, X. et al. (2015). High-resolution N(6) -methyladenosine
(m(6)A) map using photo-crosslinking-assisted m(6)A sequencing. Angew.
Chem. Int. Ed. 54: 1587–1590.
78 Hu, L., Liu, S., Peng, Y. et al. (2022). m6A RNA modications are measured at
single-base resolution across the mammalian transcriptome. Nat. Biotechnol. 40:
1210–1219.
79 Schaefer, M., Pollex, T., Hanna, K., and Lyko, F. (2009). RNA cytosine methyla-
tion analysis by bisulte sequencing. Nucleic Acids Res. 37: e12.
80 Suzuki, T., Ueda, H., Okada, S., and Sakurai, M. (2015). Transcriptome-wide
identication of adenosine-to-inosine editing using the ICE-seq method. Nat.
Protoc. 10: 715–732.
81 Li, A., Sun, X., Arguello, A.E., and Kleiner, R.E. (2022). Chemical method to
sequence 5-formylcytosine on RNA. ACS Chem. Biol. 17: 503–508.
82 Li, X., Xiong, X., Zhang, M. et al. (2017). Base-resolution mapping reveals dis-
tinct m(1)A methylome in nuclear- and mitochondrial-encoded transcripts. Mol.
Cell 68: 993–1005.e1009.
83 Liu, J., Yue, Y. , Han, D. et al. (2014). A METTL3–METTL14 complex medi-
ates mammalian nuclear RNA N6-adenosine methylation. Nat. Chem. Biol. 10:
93–95.
84 Wang, X., Feng, J., Xue, Y. et al. (2016). Structural basis of N 6-adenosine
methylation by the METTL3–METTL14 complex. Nature 534: 575–578.
References 341
https://t.me/med1917
85 Ping, X.-L., Sun, B.F., Wang, L.U. et al. (2014). Mammalian WTAP is a regula-
tory subunit of the RNA N6-methyladenosine methyltransferase. Cell Res. 24:
177–189.
86 Geula, S., Moshitch-Moshkovitz, S., Dominissini, D. et al. (2015). m6AmRNA
methylation facilitates resolution of naïve pluripotency toward dierentiation.
Science 347: 1002–1006.
87 Zhou, J., Wan, J., Gao, X. et al. (2015). Dynamic m(6)A mRNA methylation
directs translational control of heat shock response. Nature 526: 591–594.
88 Yang, X., Triboulet, R., Liu, Q. et al. (2022). Exon junction complex shapes the
m6A epitranscriptome. Nat. Commun. 13: 7904.
89 Uzonyi, A., Dierks, D., Nir, R. et al. (2023). Exclusion of m6A from splice-site
proximal regions by the exon junction complex dictates m6A topologies and
mRNA stability. Mol. Cell 83: 237–251.e237.
90 He, P.C., Wei, J., Dou, X. et al. (2023). Exon architecture controls mRNA m(6)a
suppression and gene expression. Science 379: 677–682.
91 Du, H., Zhao, Y. , He, J. et al. (2016). YTHDF2 destabilizes m6A-containing
RNA through direct recruitment of the CCR4–NOT deadenylase complex. Nat.
Commun. 7: 12626.
92 Huang, H., Weng, H., Sun, W. et al. (2018). Recognition of RNA
N(6)-methyladenosine by IGF2BP proteins enhances mRNA stability and
translation. Nat. Cell Biol. 20: 285–295.
93 Liu, J., Dou, X., Chen, C. et al. (2020). N(6)-methyladenosine of
chromosome-associated regulatory RNA regulates chromatin state and transcription. Science 367: 580–586.
94 Zaccara, S. and Jarey, S.R. (2020). A unied model for the function of YTHDF
proteins in regulating m6A-modied mRNA. Cell 181: 1582–1595.e1518.
95 Zhang, F., Kang, Y., Wang, M. et al. (2018). Fragile X mental retardation pro-
tein modulates the stability of its m6A-marked messenger RNA targets. Hum.
Mol. Genet. 27: 3936–3950.
96 Zhang, G., Xu, Y., Wang, X. et al. (2022). Dynamic FMR1 granule phase switch
instructed by m6A modication contributes to maternal RNA decay. Nat. Com-
mun. 13: 859.
97 Roost, C., Lynch, S.R., Batista, P.J. et al. (2015). Structure and thermodynamics
of N6-methyladenosine in RNA: a spring-Loaded Base modication. JACS 137:
2107–2115.
98 Dixit, D., Xie, Q., Rich, J.N., and Zhao, J.C. (2017). Messenger RNA methylation
regulates glioblastoma tumorigenesis. Cancer Cell 31: 474–475.
99 Hu, S., Tiwari, S.K., Gonzalez, G.M. et al. (2021). m6A-RNA demethylase FTO
inhibitors impair self-renewal in glioblastoma stem cells. ACS Chem. Biol. 16:
324–333.
100 He, X., Tan, L., Ni, J., and Shen, G. (2021). Expression pattern of m6Areg-
ulators is signicantly correlated with malignancy and antitumor immune
response of breast cancer. Cancer Gene Ther. 28: 188–196.
342 12 Drugging the Epitranscriptome
https://t.me/med1917
101 Singh, B., Kinne, H.E., Milligan, R.D. et al. (2016). Important role of FTO in
the survival of rare panresistant triple-negative inammatory breast cancer cells
facing a severe metabolic challenge. PLoS One 11: e0159072.
102 Xu, Y., Kinne, H.E., Milligan, R.D. et al. (2020). The FTO/miR-181b-3p/ARL5B
signaling pathway regulates cell migration and invasion in breast cancer. Cancer
Commun. (Lond) 40: 484–500.
103 Zheng, F., Du, F., Zhao, J. et al. (2021). The emerging role of RNA
N6-methyladenosine methylation in breast cancer. Biomarker Res. 9: 39.
104 Zhou, M., Dong, M., Yang, X. et al. (2022). The emerging roles and mechanism
of m6A in breast cancer progression. Front. Genet. 13.
105 Diao, M.-N., Zhang, X.-J., and Zhang, Y.-F. (2023). The critical roles of m6A
RNA methylation in lung cancer: from mechanism to prognosis and therapy. Br.
J. Cancer 129: 8–23.
106 Li, J., Han, Y., Zhang, H. et al. (2019). The m6A demethylase FTO promotes
the growth of lung cancer cells by regulating the m6A level of USP7 mRNA.
Biochem. Biophys. Res. Commun. 512: 479–485.
107 Wanna-Udom, S., Terashima, M., Lyu, H. et al. (2020). The m6A methyl-
transferase METTL3 contributes to transforming growth factor-beta-induced
epithelial-mesenchymal transition of lung cancer cells through the regulation of
JUNB. Biochem. Biophys. Res. Commun. 524: 150–155.
108 Li, Z., Weng, H., Su, R. et al. (2017). FTO plays an oncogenic role in acute
myeloid Leukemia as a N(6)-methyladenosine RNA demethylase. Cancer Cell
31: 127–141.
109 Vu, L.P., Pickering, B.F., Cheng, Y. et al. (2017). The N6-methyladenosine
(m6A)-forming enzyme METTL3 controls myeloid dierentiation of normal
hematopoietic and leukemia cells. Nat. Med. 23: 1369–1376.
110 Geng, Y., Guan, R., Hong, W. et al. (2020). Identication of m6A-related genes
and m6A RNA methylation regulators in pancreatic cancer and their association with survival. Ann. Transl. Med. 8.
111 Guo, X., Li, K., Jiang, W. et al. (2020). RNA demethylase ALKBH5 prevents
pancreatic cancer progression by posttranscriptional activation of PER1 in an
m6A-YTHDF2-dependent manner. Mol. Cancer 19: 1–19.
112 Taketo, K., Konno, M., Asai, A. et al. (2018). The epitranscriptome m6Awriter
METTL3 promotes chemo-and radioresistance in pancreatic cancer cells. Int. J.
Oncol. 52: 621–629.
113 Tang, B., Yang, Y. , Kang, M. et al. (2020). m6A demethylase ALKBH5 inhibits
pancreatic cancer tumorigenesis by decreasing WIF-1 RNA methylation and
mediating Wnt signaling. Mol. Cancer 19: 1–15.
114 Xia, T., Wu, X., Cao, M. et al. (2019). The RNA m6A methyltransferase
METTL3 promotes pancreatic cancer cell proliferation and invasion. Pathol.
Res. Pract. 215: 152666.
115 Niu, J., Wang, B., Wang, T., and Zhou, T. (2022). Mechanism of
METTL3-mediated m6A modication in depression-induced cognitive decits.
Am. J. Med. Genet. Part B: Neuropsychiatr. Genet. 189: 86–99.
References 343
https://t.me/med1917
116 Chokkalla, A.K., Mehta, S.L., and Vemuganti, R. (2020). Epitranscriptomic reg-
ulation by m6A RNA methylation in brain development and diseases. J. Cereb.
Blood Flow Metab. 40: 2331–2349.
117 Choudhry, Z., Sengupta, S.M., Grizenko, N. et al. (2013). Association between
obesity-related gene FTO and ADHD. Obesity 21: E738–E744.
118 Han, M., Liu, Z., Xu, Y. et al. (2020). Abnormality of m6A mRNA methylation
is involved in Alzheimer’s disease. Front. Neurosci. 14: 98.
119 Wu, Y. , Xie, L., Wang, M. et al. (2018). Mettl3-mediated m6A RNA methylation
regulates the fate of bone marrow mesenchymal stem cells and osteoporosis.
Nat. Commun. 9: 4772.
120 Winkler, R., Gillis, E., Lasman, L. et al. (2019). m6A modication controls
the innate immune response to infection by targeting type I interferons. Nat.
Immunol. 20: 173–182.
121 Tan, B. and Gao, S.J. (2018). RNA epitranscriptomics: regulation of infection
of RNA and DNA viruses by N6-methyladenosine (m6A). Rev. Med. Virol. 28:
e1983.
122 Wang, Y., Wang, Y., Gu, J. et al. (2022). The role of RNA m6A methylation in
lipid metabolism. Front. Endocrinol. 13: 866116.
123 Zhang, Y., Chen, W. , Zheng, X. et al. (2021). Regulatory role and mechanism
of m(6)A RNA modication in human metabolic diseases. Mol. Ther. Oncolytics
22: 52–63.
124 An, Y. and Duan, H. (2022). The role of m6A RNA methylation in cancer
metabolism. Mol. Cancer 21: 14.
125 Zeng, C., Huang, W. , Li, Y., and Weng, H. (2020). Roles of METTL3 in cancer:
mechanisms and therapeutic targeting. J. Hematol. Oncol. 13: 117.
126 Deng, L.J., Deng, W.Q., Fan, S.R. et al. (2022). m6A modication: recent
advances, anticancer targeted drug discovery and beyond. Mol. Cancer 21:
52.
127 Huang, W., Chen, T.Q., Fang, K. et al. (2021). N6-methyladenosine methyltrans-
ferases: functions, regulation, and clinical potential. J. Hematol. Oncol. 14: 117.
128 Lan, Q., Liu, P.Y., Haase, J. et al. (2019). The critical role of RNA m6A methyla-
tion in cancer. Cancer Res. 79: 1285–1292.
129 Li, X., Tang, J., Huang, W. et al. (2017). The M6A methyltransferase
METTL3: acting as a tumor suppressor in renal cell carcinoma. Oncotarget
8: 96103–96116.
130 Liu, J., Eckert, M.A., Harada, B.T. et al. (2018). m6A mRNA methylation
regulates AKT activity to promote the proliferation and tumorigenicity of
endometrial cancer. Nat. Cell Biol. 20: 1074–1083.
131 Deng, R., Cheng, Y. , Ye, S. et al. (2019). m6A methyltransferase METTL3
suppresses colorectal cancer proliferation and migration through p38/ERK
pathways. OncoTargets Ther. 12: 4391.
132 Visvanathan, A., Patil, V., Arora, A. et al. (2018). Essential role of METTL3-
mediated
radioresistance. Oncogene 37: 522–533.
m(6)A modication in glioma stem-like cells maintenance and
344 12 Drugging the Epitranscriptome
https://t.me/med1917
133 Yankova, E., Blackaby, W., Albertella, M. et al. (2021). Small-molecule inhibi-
tion of METTL3 as a strategy against myeloid leukaemia. Nature 593: 597–601.
134 Dolbois, A., Bedi, R.K., Bochenkova, E. et al. (2021).
1,4,9-Triazaspiro[5.5]undecan-2-one derivatives as potent and selective METTL3
inhibitors. J. Med. Chem. 64: 12738–12760.
135 Moroz-Omori, E.V., Huang, D., Bedi, R.K. et al. (2021). METTL3 inhibitors
for epitranscriptomic modulation of cellular processes. ChemMedChem 16:
3035–3043.
136 Bedi, R.K., Huang, D., Eberle, S.A. et al. (2020). Small-molecule inhibitors
of METTL3, the major human epitranscriptomic writer. ChemMedChem 15:
744–748.
137 STORM Therapeutics (2023). STORM Therapeutics Presents STC-15 Preclinical
Data Supporting Treatment of Patients with AML at the AACR Acute Myeloid
Leukemia and Myelodysplastic Syndrome Conference. Retrieved September 7,
2023, from https://www.stormtherapeutics.com/media/news/storm-therapeuticspresents-stc-15-preclinical-data-supporting-treatment-of-patients-with-aml-atthe-aacr-acute-myeloid.
138 STORM Therapeutics (2022). STORM Therapeutics doses rst patient with
oral METTL3 targeting drug candidate in a solid tumor Phase 1 study.
Retrieved September 7, 2023, from https://www.stormtherapeutics.com/media/
news/storm-therapeutics-doses-rst-patient-with-oral-mettl3-targeting-drugcandidate-in-a-solid-tumor-phase-1-study .
139 Ipsen. (2021) Ipsen adds another program into its pre-clinical R&D Oncology
pipeline through an exclusive worldwide collaboration with Accent Therapeutics, targeting the RNA modifying protein, METTL3. Retrieved September 7,
2023, from https://www.ipsen.com/websites/Ipsen_Online/wp-content/uploads/
2021/10/17165818/Ipsen-Accent-collaboration-18-October-2021.pdf.
140 Idrus, A.A. (2020). Fierce Biotech.
141 Wei, J., Liu, F., Lu, Z. et al. (2018). Dierential m6A, m6Am, and m1A demethy-
lation mediated by FTO in the cell nucleus and cytoplasm. Mol. Cell 71:
973–985.e975.
142 Dina, C., Meyre, D., Gallina, S. et al. (2007). Variation in FTO contributes to
childhood obesity and severe adult obesity. Nat. Genet. 39: 724–726.
143 Fischer, J., Koch, L., Emmerling, C. et al. (2009). Inactivation of the FTO gene
protects from obesity. Nature 458: 894–898.
144 Deng, X., Su, R., Stanford, S., and Chen, J. (2018). Critical enzymatic functions
of FTO in obesity and cancer. Front. Endocrinol. 9.
145 Lan, N., Lu, Y., Zhang, Y. et al. (2020). FTO – a common genetic basis for
obesity and cancer. Front. Genet. 11.
146 Fawcett, K.A. and Barroso, I. (2010). The genetics of obesity: FTO leads the
way. Trends Genet. 26: 266–274.
147 Zhou, S., Bai, Z.L., Xia, D. et al. (2018). FTO regulates the chemo-radiotherapy
resistance of cervical squamous cell carcinoma (CSCC) by targeting β-catenin
through mRNA demethylation. Mol. Carcinog. 57: 590–597.
Соседние файлы в папке Библиотека им академика М.И. Перельмана