Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6AHPVG)

• DOT Name: Ribosome-recycling factor, mitochondrial (MRRF)
• Synonyms: RRF; mtRRF; Ribosome-releasing factor, mitochondrial
• Gene Name: MRRF
• Related Disease:
  Cytochrome-c oxidase deficiency disease
  Mitochondrial trifunctional protein deficiency
  Myopathy
• UniProt ID: RRFM_HUMAN
• PDB ID: 6NU2; 6ZS9; 7L08; 7L20; 7NSH; 7NSI
• Pfam ID: PF01765
• Sequence:
  MALGLKCFRMVHPTFRNYLAASIRPVSEVTLKTVHERQHGHRQYMAYSAVPVRHFATKKA
  KAKGKGQSQTRVNINAALVEDIINLEEVNEEMKSVIEALKDNFNKTLNIRTSPGSLDKIA
  VVTADGKLALNQISQISMKSPQLILVNMASFPECTAAAIKAIRESGMNLNPEVEGTLIRV
  PIPQVTREHREMLVKLAKQNTNKAKDSLRKVRTNSMNKLKKSKDTVSEDTIRLIEKQISQ
  MADDTVAELDRHLAVKTKELLG
• Function: Responsible for the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis. Acts in collaboration with GFM2. Promotes mitochondrial ribosome recycling by dissolution of intersubunit contacts.
• Reactome Pathway: Mitochondrial translation termination (R-HSA-5419276)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cytochrome-c oxidase deficiency disease	DISK7N3G	Strong	Biomarker	[1]
Mitochondrial trifunctional protein deficiency	DIS2MYYR	Strong	Altered Expression	[2]
Myopathy	DISOWG27	Strong	Altered Expression	[3]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Ribosome-recycling factor, mitochondrial (MRRF).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ribosome-recycling factor, mitochondrial (MRRF).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Ribosome-recycling factor, mitochondrial (MRRF).	[6]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Ribosome-recycling factor, mitochondrial (MRRF).	[7]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Ribosome-recycling factor, mitochondrial (MRRF).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ribosome-recycling factor, mitochondrial (MRRF).	[9]

References

• [1] Mitochondrial DNA depletion syndrome due to mutations in the RRM2B gene.Neuromuscul Disord. 2008 Jun;18(6):453-9. doi: 10.1016/j.nmd.2008.04.006. Epub 2008 May 27.
• [2] A diagnostic algorithm for metabolic myopathies.Curr Neurol Neurosci Rep. 2010 Mar;10(2):118-26. doi: 10.1007/s11910-010-0096-4.
• [3] Abnormal levels of human mitochondrial transcription factor A in skeletal muscle in mitochondrial encephalomyopathies.Neurol Sci. 2000;21(5 Suppl):S985-7. doi: 10.1007/s100720070017.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
• [8] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.