MRRF

Summary

MRRF (mitochondrial ribosome recycling factor, HGNC:7234) is a protein-coding gene on chromosome 9q33.2, encoding Ribosome-recycling factor, mitochondrial (Q96E11). Responsible for the disassembly of ribosomes from messenger RNA at the termination of mitochondrial protein biosynthesis.

This gene encodes a ribosome recycling factor, which is a component of the mitochondrial translational machinery. The encoded protein, along with mitochondrial elongation factor 2, functions in ribosomal recycling at the termination of mitochondrial translation by mediating the disassembly of ribosomes from messenger RNA. A pseudogene of this gene has been identified on chromosome X.

Source: NCBI Gene 92399 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 52 total
• MANE Select transcript: NM_138777

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7234
Approved symbol	MRRF
Name	mitochondrial ribosome recycling factor
Location	9q33.2
Locus type	gene with protein product
Status	Approved
Aliases	RRF
Ensembl gene	ENSG00000148187
Ensembl biotype	protein_coding
OMIM	604602
Entrez	92399

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 13 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000297908, ENST00000344641, ENST00000373723, ENST00000373724, ENST00000373727, ENST00000373728, ENST00000373729, ENST00000394315, ENST00000441707, ENST00000467864, ENST00000470366, ENST00000489572, ENST00000870638, ENST00000870639, ENST00000870640, ENST00000870641, ENST00000938375, ENST00000948156, ENST00000948157

RefSeq mRNA: 8 — MANE Select: NM_138777 NM_001173512, NM_001346339, NM_001346341, NM_001346343, NM_001346345, NM_001346347, NM_138777, NM_199177

CCDS: CCDS48013, CCDS55336, CCDS6840, CCDS87684

Canonical transcript exons

ENST00000344641 — 7 exons

Exon	Start	End
ENSE00001390026	122322540	122331337
ENSE00001461421	122264882	122264938
ENSE00003520955	122313227	122313386
ENSE00003628261	122291749	122291840
ENSE00003707804	122280443	122280598
ENSE00003708440	122270864	122271075
ENSE00003784808	122285169	122285287

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 94.82.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.2767 / max 177.2784, expressed in 1813 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98402	19.9836	1809
98403	1.9499	1037
98401	0.3432	166

Top tissues by expression

242 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
rectum	UBERON:0001052	94.82	gold quality
pancreatic ductal cell	CL:0002079	94.14	silver quality
lower esophagus mucosa	UBERON:0035834	93.65	gold quality
left testis	UBERON:0004533	93.63	gold quality
metanephros cortex	UBERON:0010533	93.40	gold quality
right testis	UBERON:0004534	93.37	gold quality
mucosa of transverse colon	UBERON:0004991	93.00	gold quality
right uterine tube	UBERON:0001302	92.92	gold quality
gastrocnemius	UBERON:0001388	92.78	gold quality
muscle of leg	UBERON:0001383	92.59	gold quality
transverse colon	UBERON:0001157	92.49	gold quality
right lobe of liver	UBERON:0001114	92.18	gold quality
left lobe of thyroid gland	UBERON:0001120	91.78	gold quality
right lobe of thyroid gland	UBERON:0001119	91.77	gold quality
apex of heart	UBERON:0002098	91.71	gold quality
body of pancreas	UBERON:0001150	91.70	gold quality
esophagus mucosa	UBERON:0002469	91.69	gold quality
skin of leg	UBERON:0001511	91.60	gold quality
mucosa of stomach	UBERON:0001199	91.49	gold quality
skin of abdomen	UBERON:0001416	91.49	gold quality
small intestine Peyer’s patch	UBERON:0003454	91.41	gold quality
islet of Langerhans	UBERON:0000006	91.30	gold quality
hindlimb stylopod muscle	UBERON:0004252	91.29	gold quality
esophagus	UBERON:0001043	91.05	gold quality
heart left ventricle	UBERON:0002084	90.97	gold quality
thyroid gland	UBERON:0002046	90.96	gold quality
muscle layer of sigmoid colon	UBERON:0035805	90.92	gold quality
testis	UBERON:0000473	90.88	gold quality
right adrenal gland	UBERON:0001233	90.85	gold quality
right atrium auricular region	UBERON:0006631	90.69	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

51 targeting MRRF, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-519A-3P	99.67	71.67	1868
HSA-MIR-519B-3P	99.67	71.67	1868
HSA-MIR-519C-3P	99.67	71.67	1870
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-3682-3P	99.58	67.63	865
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-3182	99.40	68.15	2454
HSA-MIR-3606-5P	99.31	69.67	1168
HSA-MIR-196A-3P	99.19	67.34	1204
HSA-MIR-7151-3P	99.04	69.72	2370
HSA-MIR-628-3P	99.04	68.37	814
HSA-MIR-6737-3P	98.95	68.56	1577

Literature-anchored findings (GeneRIF, showing 2)

• Depletion of mtRRF in human cell lines is lethal, initially causing profound mitochondrial dysmorphism, aggregation of mitoribosomes and elevated mitochondrial superoxide production. (PMID:18782833)
• EF-G2mt is an exclusive recycling factor in mammalian mitochondrial protein synthesis. (PMID:19716793)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mrrf	ENSDARG00000034174
mus_musculus	Mrrf	ENSMUSG00000026887
rattus_norvegicus	Mrrf	ENSRNOG00000025997
drosophila_melanogaster	mRRF1	FBGN0035980
caenorhabditis_elegans	mrrf-1	WBGENE00020625

Protein

Protein identifiers

Ribosome-recycling factor, mitochondrial — Q96E11 (reviewed: Q96E11)

Alternative names: Ribosome-releasing factor, mitochondrial

All UniProt accessions (2): Q96E11, X6RDS5

UniProt curated annotations — full annotation on UniProt →

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.

Subcellular location. Mitochondrion.

Similarity. Belongs to the RRF family.

Isoforms (8)

UniProt ID	Names	Canonical?
Q96E11-1	1	yes
Q96E11-2	2
Q96E11-3	3
Q96E11-4	4
Q96E11-5	5
Q96E11-6	6
Q96E11-7	7
Q96E11-8	8

RefSeq proteins (8): NP_001166983, NP_001333268, NP_001333270, NP_001333272, NP_001333274, NP_001333276, NP_620132, NP_954646 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002661	Ribosome_recyc_fac	Family
IPR023584	Ribosome_recyc_fac_dom	Domain
IPR036191	RRF_sf	Homologous_superfamily

Pfam: PF01765

UniProt features (12 total): splice variant 9, transit peptide 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
7L20	ELECTRON MICROSCOPY	3.15
7NSH	ELECTRON MICROSCOPY	3.2
7L08	ELECTRON MICROSCOPY	3.49
6NU2	ELECTRON MICROSCOPY	3.9
6ZS9	ELECTRON MICROSCOPY	4
7NSI	ELECTRON MICROSCOPY	4.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96E11-F1	78.38	0.45

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-5419276	Mitochondrial translation termination
R-HSA-392499	Metabolism of proteins
R-HSA-5368287	Mitochondrial translation
R-HSA-72766	Translation

MSigDB gene sets: 121 (showing top): GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_TRANSLATION, CREB_Q4, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, CREB_Q2_01, ATF4_Q2, MODULE_207, GOBP_ORGANELLE_DISASSEMBLY, CREBP1CJUN_01, CREB_01, GOCC_MITOCHONDRIAL_MATRIX, CGTSACG_PAX3_B, TGACGTCA_ATF3_Q6, CCGNMNNTNACG_UNKNOWN

GO Biological Process (2): translation (GO:0006412), ribosome disassembly (GO:0032790)

GO Molecular Function (2): ribosomal large subunit binding (GO:0043023), protein binding (GO:0005515)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Mitochondrial translation	1
Translation	1
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
peptidyltransferase activity	1
translational initiation	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
organelle disassembly	1
ribosome binding	1
binding	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

3188 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MRRF	GFM2	Q969S9	990
MRRF	GFM1	Q96RP9	967
MRRF	TSFM	P43897	866
MRRF	ABCE1	P61221	811
MRRF	EIF5B	O60841	810
MRRF	TUFM	P49411	755
MRRF	GTPBP2	Q9BX10	751
MRRF	EEF2	P13639	727
MRRF	MIEF2	Q96C03	710
MRRF	MTRF1	O75570	706
MRRF	MTRF1L	Q9UGC7	705
MRRF	MTIF2	P46199	689
MRRF	ATP5IF1	Q9UII2	677
MRRF	HBS1L	Q9Y450	656
MRRF	MRPL58	Q14197	649

IntAct

52 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
MRRF	DBT	psi-mi:“MI:0914”(association)	0.620
MRRF	DBT	psi-mi:“MI:0915”(physical association)	0.620
KRT40	MRRF	psi-mi:“MI:0915”(physical association)	0.560
CMTM5	MRRF	psi-mi:“MI:0915”(physical association)	0.560
BANP	MRRF	psi-mi:“MI:0915”(physical association)	0.560
FHL3	MRRF	psi-mi:“MI:0915”(physical association)	0.560
SYP	MRRF	psi-mi:“MI:0915”(physical association)	0.560
MRRF	WIPI2	psi-mi:“MI:0915”(physical association)	0.560
MRRF	ZNF408	psi-mi:“MI:0915”(physical association)	0.560
FAM9B	MRRF	psi-mi:“MI:0915”(physical association)	0.560
AGTRAP	MRRF	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	MRRF	psi-mi:“MI:0915”(physical association)	0.550
CT55	BLTP3B	psi-mi:“MI:0914”(association)	0.530
EFNB2	MRRF	psi-mi:“MI:0915”(physical association)	0.400
HCCS	MPZL1	psi-mi:“MI:0914”(association)	0.350
SOCS6	USP1	psi-mi:“MI:0914”(association)	0.350
AHR	SHTN1	psi-mi:“MI:0914”(association)	0.350
MRM2	VWA8	psi-mi:“MI:0914”(association)	0.350
ZNF8	METTL15	psi-mi:“MI:0914”(association)	0.350
FGFR1OP2	METTL15	psi-mi:“MI:0914”(association)	0.350
NUDT13	PLPBP	psi-mi:“MI:0914”(association)	0.350
ZNF501	PCK1	psi-mi:“MI:0914”(association)	0.350
NAT1	MRRF	psi-mi:“MI:0914”(association)	0.350
MTIF3	SEMG1	psi-mi:“MI:0914”(association)	0.350
DCN	CHSY3	psi-mi:“MI:0914”(association)	0.350

BioGRID (343): MRRF (Affinity Capture-MS), MRRFP1 (Affinity Capture-MS), DBT (Affinity Capture-MS), MMAB (Affinity Capture-MS), NFS1 (Affinity Capture-MS), LYRM7 (Affinity Capture-MS), IBA57 (Affinity Capture-MS), MRRF (Affinity Capture-MS), MRRF (Two-hybrid), MRRF (Affinity Capture-MS), MRRF (Affinity Capture-MS), MRRF (Affinity Capture-MS), MRRF (Affinity Capture-MS), MRRF (Affinity Capture-MS), MRRF (Affinity Capture-MS)

ESM2 similar proteins: A0JN27, A8MXK1, B0CM95, B0KWE9, B2KI79, O42602, O62657, P40224, P48061, P55244, Q0VCQ4, Q12841, Q13888, Q15303, Q1JQE6, Q2KJ29, Q2TBV5, Q3KNV8, Q3ZCD7, Q3ZCW2, Q58D84, Q5EA19, Q5R5K6, Q5R8Y5, Q5R9Y1, Q5RFN0, Q5RKI9, Q61527, Q62956, Q6ICL3, Q6P1K8, Q6PIU2, Q8BGR6, Q8BLF1, Q8BTQ0, Q8BZI6, Q8VDI9, Q8VED9, Q90986, Q91ZH7

Diamond homologs: A0L8Q8, A1B966, A1KRL9, A3DE56, A3PJF7, A4FMD4, A4JF72, A4SYU8, A4W6R7, A4WUH8, A5I4K9, A5ICK7, A5UUU9, A5V3G5, A6SZP8, A6TRM0, A6U8K5, A7FFH2, A7FPZ5, A7GG20, A7HY16, A7INR3, A7MXZ7, A7NQW5, A8GIE3, A8MHH2, A9BMM9, A9GGK7, A9HKW6, A9WAG2, B0SZ18, B1II63, B1LTQ4, B1XTU6, B2UKL9, B2VE11, B3PYP5, B4F2D0, B4RBZ1, B5F9X3

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

52 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1556 predictions. Top by Δscore:

Variant	Effect	Δscore
9:122264710:CTCA:C	donor_loss	1.0000
9:122264711:TCAC:T	donor_loss	1.0000
9:122264712:CACCT:C	donor_loss	1.0000
9:122264713:ACCTC:A	donor_loss	1.0000
9:122265542:C:CG	donor_gain	1.0000
9:122265542:C:G	donor_gain	1.0000
9:122265547:T:G	donor_gain	1.0000
9:122270862:A:AG	acceptor_gain	1.0000
9:122270862:AGT:A	acceptor_gain	1.0000
9:122270862:AGTG:A	acceptor_gain	1.0000
9:122270863:G:GG	acceptor_gain	1.0000
9:122270863:GT:G	acceptor_gain	1.0000
9:122270863:GTG:G	acceptor_gain	1.0000
9:122270863:GTGG:G	acceptor_gain	1.0000
9:122280441:A:AG	acceptor_gain	1.0000
9:122280442:G:GG	acceptor_gain	1.0000
9:122280594:ACCAG:A	donor_loss	1.0000
9:122280596:CAGG:C	donor_loss	1.0000
9:122280597:AGGTT:A	donor_loss	1.0000
9:122280599:G:C	donor_loss	1.0000
9:122280600:T:A	donor_loss	1.0000
9:122285164:TTTA:T	acceptor_loss	1.0000
9:122285166:TA:T	acceptor_loss	1.0000
9:122285167:A:AG	acceptor_gain	1.0000
9:122285167:AG:A	acceptor_gain	1.0000
9:122285168:G:GG	acceptor_gain	1.0000
9:122285168:GG:G	acceptor_gain	1.0000
9:122285168:GGA:G	acceptor_gain	1.0000
9:122285168:GGAT:G	acceptor_gain	1.0000
9:122285168:GGATC:G	acceptor_gain	1.0000

AlphaMissense

1724 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:122313245:A:C	R190S	0.992
9:122313245:A:T	R190S	0.992
9:122291774:T:A	I162K	0.991
9:122313265:C:A	A197D	0.991
9:122313264:G:C	A197P	0.990
9:122291770:G:C	A161P	0.989
9:122313301:G:C	R209P	0.989
9:122322607:T:C	L260P	0.989
9:122322596:G:C	K256N	0.988
9:122322596:G:T	K256N	0.988
9:122291774:T:G	I162R	0.987
9:122291828:T:A	V180E	0.987
9:122313310:G:C	R212P	0.987
9:122285228:A:C	S134R	0.986
9:122285230:C:A	S134R	0.986
9:122285230:C:G	S134R	0.986
9:122285265:T:A	V146E	0.986
9:122313290:A:C	K205N	0.986
9:122313290:A:T	K205N	0.986
9:122285217:T:C	L130S	0.985
9:122291762:C:A	A158D	0.984
9:122291822:T:A	I178N	0.984
9:122291822:T:C	I178T	0.984
9:122280554:T:C	L99P	0.982
9:122285256:T:C	L143P	0.982
9:122313244:G:C	R190T	0.982
9:122291774:T:C	I162T	0.981
9:122313285:G:C	A204P	0.981
9:122291822:T:G	I178S	0.980
9:122291795:T:C	L169P	0.978

dbSNP variants (sampled 300 via entrez): RS1000013414 (9:122319242 C>G,T), RS1000146984 (9:122267875 A>G), RS1000159453 (9:122295441 C>G), RS1000277864 (9:122267513 C>G), RS1000283246 (9:122288268 A>C), RS1000310839 (9:122302393 T>C,G), RS1000350388 (9:122264147 T>C), RS1000389367 (9:122316269 G>A), RS1000425441 (9:122263860 T>C), RS1000449694 (9:122319600 A>G), RS1000515687 (9:122301256 A>C), RS1000563929 (9:122302098 G>A), RS1000582526 (9:122308358 T>C), RS1000593106 (9:122301744 T>C), RS1000649924 (9:122300959 G>A)

Disease associations

OMIM: gene MIM:604602 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, decreases methylation, affects cotreatment	4
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	3
Tretinoin	decreases expression	2
Thapsigargin	decreases expression, increases reaction, increases expression	2
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
bisphenol A	decreases expression	1
arsenite	affects binding, increases reaction	1
manganese chloride	increases abundance, increases expression	1
methacrylaldehyde	increases expression, increases abundance, affects cotreatment	1
caffeic acid	decreases expression, increases reaction	1
4-methoxycinnamate methyl ester	decreases expression, increases reaction	1
CGP 52608	affects binding, increases reaction	1
corosolic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Vorinostat	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Drugs, Chinese Herbal	decreases expression, increases reaction	1
Formaldehyde	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Manganese	increases abundance, increases expression	1
Ozone	increases expression, increases abundance, affects cotreatment	1
Phthalic Acids	decreases methylation	1
Tunicamycin	increases expression	1
Vanadates	decreases expression	1

Clinical trials (associated diseases)

5 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis