Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQI1AR1)

• DOT Name: RNA-binding protein 24 (RBM24)
• Synonyms: RNA-binding motif protein 24; RNA-binding region-containing protein 6
• Gene Name: RBM24
• Related Disease:
  Cardiac failure
  Cardiomyopathy
  Congestive heart failure
  Dilated cardiomyopathy
  Dilated cardiomyopathy 1A
  Hepatitis B virus infection
  Hepatitis C virus infection
  Riley-Day syndrome
  Congenital heart disease
  Microphthalmia
  Nasopharyngeal carcinoma
  Neoplasm
• UniProt ID: RBM24_HUMAN
• Pfam ID: PF00076
• Sequence:
  MHTTQKDTTYTKIFVGGLPYHTTDASLRKYFEVFGEIEEAVVITDRQTGKSRGYGFVTMA
  DRAAAERACKDPNPIIDGRKANVNLAYLGAKPRIMQPGFAFGVQQLHPALIQRPFGIPAH
  YVYPQAFVQPGVVIPHVQPTAAAASTTPYIDYTGAAYAQYSAAAAAAAAAAAYDQYPYAA
  SPAAAGYVTAGGYGYAVQQPITAAAPGTAAAAAAAAAAAAAFGQYQPQQLQTDRMQ
• Function: Multifunctional RNA-binding protein involved in the regulation of pre-mRNA splicing, mRNA stability and mRNA translation important for cell fate decision and differentiation. Plays a major role in pre-mRNA alternative splicing regulation. Mediates preferentially muscle-specific exon inclusion in numerous mRNAs important for striated cardiac and skeletal muscle cell differentiation. Binds to intronic splicing enhancer (ISE) composed of stretches of GU-rich motifs localized in flanking intron of exon that will be included by alternative splicing. Involved in embryonic stem cell (ESC) transition to cardiac cell differentiation by promoting pre-mRNA alternative splicing events of several pluripotency and/or differentiation genes. Plays a role in the regulation of mRNA stability. Binds to 3'-untranslated region (UTR) AU-rich elements in target transcripts, such as CDKN1A and MYOG, leading to maintain their stabilities. Involved in myogenic differentiation by regulating MYOG levels. Binds to multiple regions in the mRNA 3'-UTR of TP63 isoform 2, hence inducing its destabilization. Promotes also the destabilization of the CHRM2 mRNA via its binding to a region in the coding sequence. Plays a role in the regulation of mRNA translation. Mediates repression of p53/TP53 mRNA translation through its binding to U-rich element in the 3'-UTR, hence preventing EIF4E from binding to p53/TP53 mRNA and translation initiation. Binds to a huge amount of mRNAs. Required for embryonic heart development, sarcomer and M-band formation in striated muscles. Together with RBM20, promotes the expression of short isoforms of PDLIM5/ENH in cardiomyocytes; (Microbial infection) Promotes hepatitis C virus (HCV) replication over translation through the inhibition of viral protein expression. Decreases viral translation by linking viral 5'- and 3'-UTRs, blocking 80S ribosome assembly on the viral IRES and enhancing the interaction of the mature core protein and 5'-UTR.
• Tissue Specificity: Expressed in fetal and adult heart and skeletal muscles .

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Strong	Biomarker	[1]
Cardiomyopathy	DISUPZRG	Strong	Biomarker	[1]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[1]
Dilated cardiomyopathy	DISX608J	Strong	Biomarker	[1]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[1]
Hepatitis B virus infection	DISLQ2XY	Strong	Biomarker	[2]
Hepatitis C virus infection	DISQ0M8R	Strong	Biomarker	[3]
Riley-Day syndrome	DISJZHNP	Strong	Biomarker	[4]
Congenital heart disease	DISQBA23	Limited	Biomarker	[5]
Microphthalmia	DISGEBES	Limited	Altered Expression	[6]
Nasopharyngeal carcinoma	DISAOTQ0	Limited	Altered Expression	[7]
Neoplasm	DISZKGEW	Limited	Biomarker	[7]

24 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of RNA-binding protein 24 (RBM24).	[8]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of RNA-binding protein 24 (RBM24).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of RNA-binding protein 24 (RBM24).	[10]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of RNA-binding protein 24 (RBM24).	[11]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of RNA-binding protein 24 (RBM24).	[12]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of RNA-binding protein 24 (RBM24).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of RNA-binding protein 24 (RBM24).	[13]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of RNA-binding protein 24 (RBM24).	[14]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of RNA-binding protein 24 (RBM24).	[15]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of RNA-binding protein 24 (RBM24).	[16]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of RNA-binding protein 24 (RBM24).	[17]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of RNA-binding protein 24 (RBM24).	[18]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of RNA-binding protein 24 (RBM24).	[19]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of RNA-binding protein 24 (RBM24).	[20]
Irinotecan	DMP6SC2	Approved	Irinotecan increases the expression of RNA-binding protein 24 (RBM24).	[21]
Ethinyl estradiol	DMODJ40	Approved	Ethinyl estradiol increases the expression of RNA-binding protein 24 (RBM24).	[22]
Melphalan	DMOLNHF	Approved	Melphalan increases the expression of RNA-binding protein 24 (RBM24).	[23]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of RNA-binding protein 24 (RBM24).	[24]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of RNA-binding protein 24 (RBM24).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of RNA-binding protein 24 (RBM24).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of RNA-binding protein 24 (RBM24).	[25]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of RNA-binding protein 24 (RBM24).	[26]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of RNA-binding protein 24 (RBM24).	[27]
OXYQUINOLINE	DMZVS9Y	Investigative	OXYQUINOLINE increases the expression of RNA-binding protein 24 (RBM24).	[13]

References

• [1] RNA binding protein 24 deletion disrupts global alternative splicing and causes dilated cardiomyopathy.Protein Cell. 2019 Jun;10(6):405-416. doi: 10.1007/s13238-018-0578-8. Epub 2018 Sep 28.
• [2] RNA-Binding Motif Protein 24 (RBM24) Is Involved in Pregenomic RNA Packaging by Mediating Interaction between Hepatitis B Virus Polymerase and the Epsilon Element.J Virol. 2019 Mar 5;93(6):e02161-18. doi: 10.1128/JVI.02161-18. Print 2019 Mar 15.
• [3] RNA binding protein 24 regulates the translation and replication of hepatitis C virus.Protein Cell. 2018 Nov;9(11):930-944. doi: 10.1007/s13238-018-0507-x. Epub 2018 Jan 30.
• [4] RBM24 promotes U1 snRNP recognition of the mutated 5' splice site in the IKBKAP gene of familial dysautonomia.RNA. 2017 Sep;23(9):1393-1403. doi: 10.1261/rna.059428.116. Epub 2017 Jun 7.
• [5] Rbm24, a target of p53, is necessary for proper expression of p53 and heart development.Cell Death Differ. 2018 Jun;25(6):1118-1130. doi: 10.1038/s41418-017-0029-8. Epub 2018 Jan 22.
• [6] The master transcription factor SOX2, mutated in anophthalmia/microphthalmia, is post-transcriptionally regulated by the conserved RNA-binding protein RBM24 in vertebrate eye development.Hum Mol Genet. 2020 Mar 13;29(4):591-604. doi: 10.1093/hmg/ddz278.
• [7] RBM24 suppresses cancer progression by upregulating miR-25 to target MALAT1 in nasopharyngeal carcinoma.Cell Death Dis. 2016 Sep 1;7(9):e2352. doi: 10.1038/cddis.2016.252.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [10] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [11] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [12] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [13] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [14] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [15] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [16] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [17] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [18] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [19] Gene expression profiling in Ishikawa cells: a fingerprint for estrogen active compounds. Toxicol Appl Pharmacol. 2009 Apr 1;236(1):85-96.
• [20] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [21] Clinical determinants of response to irinotecan-based therapy derived from cell line models. Clin Cancer Res. 2008 Oct 15;14(20):6647-55.
• [22] The genomic response of a human uterine endometrial adenocarcinoma cell line to 17alpha-ethynyl estradiol. Toxicol Sci. 2009 Jan;107(1):40-55.
• [23] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [24] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [25] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [26] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [27] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.