Ribosome recycling factor

MRRF
Identifiers
Aliases	MRRF, MRFF, MTRRF, RRF, mitochondrial ribosome recycling factor
External IDs	OMIM: 604602; MGI: 1915121; HomoloGene: 12203; GeneCards: MRRF; OMA:MRRF - orthologs
Gene location (Human)
Chr.	Chromosome 9 (human)
End	122,331,337 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	36,080,659 bp
RNA expression pattern
	Top expressed in
	rectum; ; left testis; ; right testis; ; mucosa of transverse colon; ; right uterine tube; ; gastrocnemius muscle; ; right lobe of liver; ; left lobe of thyroid gland; ; right lobe of thyroid gland; ; apex of heart;
	Top expressed in
	tail of embryo; ; genital tubercle; ; interventricular septum; ; endothelial cell of lymphatic vessel; ; Paneth cell; ; spermatid; ; external carotid artery; ; condyle; ; muscle of thigh; ; left lobe of liver;
	More reference expression data
	n/a
Gene ontology
Molecular function	ribosomal large subunit binding;
Cellular component	mitochondrial matrix; mitochondrion;
Biological process	ribosome disassembly; protein biosynthesis; mitochondrial translational termination;
	Sources:Amigo / QuickGO
Orthologs
	92399
	67871
	ENSG00000148187
	ENSMUSG00000026887
	Q96E11
	Q9D6S7
NM_001173512; NM_138777; NM_199176; NM_199177; NM_001346339;
	NM_001346341; NM_001346343; NM_001346345; NM_001346347
	NM_026422
NP_001166983; NP_001333268; NP_001333270; NP_001333272; NP_001333274;
	NP_001333276; NP_620132; NP_954646
	NP_080698
	Wikidata
View/Edit Human	View/Edit Mouse

Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Ribosome recycling factor
Ribosome recycling factor
Identifiers
Symbol	RRF
Pfam	PF01765
InterPro	IPR002661
CATH	1ek8
SCOP2	1ek8 / SCOPe / SUPFAM
CDD	cd00520
Pfam
Available protein structures:
Pfam	structures / ECOD
PDB	RCSB PDB; PDBe; PDBj
PDBsum	structure summary

Ribosome recycling factor or ribosome release factor (RRF) is a protein found in bacterial cells as well as eukaryotic organelles, specifically mitochondria and chloroplasts. It functions to recycle ribosomes after completion of protein synthesis (bacterial translation). In humans, the mitochrondrial version is coded by the MRRF gene.

Discovery

The ribosome recycling factor was discovered in the early 1970s by the work of Akira Kaji and Akikazu Hiroshima at the University of Pennsylvania.^[5]^[6]^[7]^[8] Their work described the requirement for two protein factors to release ribosomes from mRNA. These two factors were identified as RRF, an unknown protein until then, and Elongation Factor G (EF-G), a protein already identified and known to function in protein synthesis. RRF was originally called Ribosome Releasing Factor but is now called Ribosome Recycling Factor.

Function

RRF accomplishes the recycling of ribosomes by splitting ribosomes into subunits, thereby releasing the bound mRNA. This also requires the participation of EF-G (GFM2 in humans).^[9] Depending on the tRNA, IF1–IF3 may also perform recycling.^[10]

Loss of RRF function

In Bacteria (specifically Escherichia coli), loss of the gene encoding RRF is deleterious.^[11] This makes RRF a possible target for new antibacterial drugs.
Yeast mitochondrial RRF (mtRRF) is encoded by a gene in the cell nucleus. Loss of function of this gene leads to mitochondrial genome instability and respiratory incompetence.^[12]

Structure and binding to ribosomes

The crystal structure of RRF was first determined by X-ray diffraction in 1999.^[13] The most striking revelation was that RRF is a near-perfect structural mimic of tRNA, in both size and dimensions. One view of RRF can be seen here.

Despite the tRNA-mimicry, RRF binds to ribosomes quite differently from the way tRNA does.^[14] It has been suggested that ribosomes bind proteins (or protein domain) of similar shape and size to tRNA, and this, rather than function, explains the observed structural mimicry.

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000148187 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000026887 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Hirashima A, Kaji A (November 1970). "Factor dependent breakdown of polysomes". Biochem. Biophys. Res. Commun. 41 (4): 877–883. doi:10.1016/0006-291X(70)90165-8. PMID 4920474.
^ Hirashima A, Kaji A (March 1972). "Factor-dependent release of ribosomes from messenger RNA. Requirement for two heat-stable factors". J. Mol. Biol. 65 (1): 43–58. doi:10.1016/0022-2836(72)90490-1. PMID 4553259.
^ Hirashima A, Kaji A (October 1972). "Purification and properties of ribosome-releasing factor". Biochemistry. 11 (22): 4037–4044. doi:10.1021/bi00772a005. PMID 4563926.
^ Hirashima A, Kaji A (November 1973). "Role of elongation factor G and a protein factor on the release of ribosomes from messenger ribonucleic acid". J. Biol. Chem. 248 (21): 7580–7587. doi:10.1016/S0021-9258(19)43330-9. PMID 4583357.
^ Hirokawa G, Demeshkina N, Iwakura N, Kaji H, Kaji A (March 2006). "The ribosome-recycling step: Consensus or controversy?". Trends Biochem. Sci. 31 (3): 143–149. doi:10.1016/j.tibs.2006.01.007. PMID 16487710.
^ Pavlov, MY; Antoun, A; Lovmar, M; Ehrenberg, M (18 June 2008). "Complementary roles of initiation factor 1 and ribosome recycling factor in 70S ribosome splitting". The EMBO Journal. 27 (12): 1706–17. doi:10.1038/emboj.2008.99. PMC 2435134. PMID 18497739.
^ Janosi L, Shimizu I, Kaji A (May 1994). "Ribosome recycling factor (ribosome releasing factor) is essential for bacterial growth". Proc. Natl. Acad. Sci. U.S.A. 91 (10): 4249–4253. Bibcode:1994PNAS...91.4249J. doi:10.1073/pnas.91.10.4249. PMC 43762. PMID 8183897.
^ Teyssier E, Hirokawa G, Tretiakova A, Jameson B, Kaji A, Kaji H (July 2003). "Temperature-sensitive mutation in yeast mitochondrial ribosome recycling factor (RRF)". Nucleic Acids Res. 31 (14): 4218–4226. doi:10.1093/nar/gkg449. PMC 165964. PMID 12853640.
^ Selmer M, Al-Karadaghi S, Hirokawa G, Kaji A, Liljas A (December 1999). "Crystal structure of Thermotoga maritima ribosome recycling factor: a tRNA mimic". Science. 286 (5448): 2349–2352. doi:10.1126/science.286.5448.2349. PMID 10600747.
^ Agrawal RK, Sharma MR, Kiel MC, et al. (June 2004). "Visualization of ribosome-recycling factor on the Escherichia coli 70S ribosome: functional implications". Proc. Natl. Acad. Sci. U.S.A. 101 (24): 8900–8905. Bibcode:2004PNAS..101.8900A. doi:10.1073/pnas.0401904101. PMC 428444. PMID 15178758.

External links

ribosome+releasing+factor at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
Bao, Letian (2022-11-01). "Rate-limiting hydrolysis in ribosomal release reactions revealed by ester activation". Journal of Biological Chemistry. 298 (11): 102509. doi:10.1016/j.jbc.2022.102509.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000148187 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000026887 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Hirashima A, Kaji A (November 1970). "Factor dependent breakdown of polysomes". Biochem. Biophys. Res. Commun. 41 (4): 877–883. doi:10.1016/0006-291X(70)90165-8. PMID 4920474.

[6] Hirashima A, Kaji A (March 1972). "Factor-dependent release of ribosomes from messenger RNA. Requirement for two heat-stable factors". J. Mol. Biol. 65 (1): 43–58. doi:10.1016/0022-2836(72)90490-1. PMID 4553259.

[7] Hirashima A, Kaji A (October 1972). "Purification and properties of ribosome-releasing factor". Biochemistry. 11 (22): 4037–4044. doi:10.1021/bi00772a005. PMID 4563926.

[8] Hirashima A, Kaji A (November 1973). "Role of elongation factor G and a protein factor on the release of ribosomes from messenger ribonucleic acid". J. Biol. Chem. 248 (21): 7580–7587. doi:10.1016/S0021-9258(19)43330-9. PMID 4583357.

[9] Hirokawa G, Demeshkina N, Iwakura N, Kaji H, Kaji A (March 2006). "The ribosome-recycling step: Consensus or controversy?". Trends Biochem. Sci. 31 (3): 143–149. doi:10.1016/j.tibs.2006.01.007. PMID 16487710.

[10] Pavlov, MY; Antoun, A; Lovmar, M; Ehrenberg, M (18 June 2008). "Complementary roles of initiation factor 1 and ribosome recycling factor in 70S ribosome splitting". The EMBO Journal. 27 (12): 1706–17. doi:10.1038/emboj.2008.99. PMC 2435134. PMID 18497739.

[11] Janosi L, Shimizu I, Kaji A (May 1994). "Ribosome recycling factor (ribosome releasing factor) is essential for bacterial growth". Proc. Natl. Acad. Sci. U.S.A. 91 (10): 4249–4253. Bibcode:1994PNAS...91.4249J. doi:10.1073/pnas.91.10.4249. PMC 43762. PMID 8183897.

[12] Teyssier E, Hirokawa G, Tretiakova A, Jameson B, Kaji A, Kaji H (July 2003). "Temperature-sensitive mutation in yeast mitochondrial ribosome recycling factor (RRF)". Nucleic Acids Res. 31 (14): 4218–4226. doi:10.1093/nar/gkg449. PMC 165964. PMID 12853640.

[13] Selmer M, Al-Karadaghi S, Hirokawa G, Kaji A, Liljas A (December 1999). "Crystal structure of Thermotoga maritima ribosome recycling factor: a tRNA mimic". Science. 286 (5448): 2349–2352. doi:10.1126/science.286.5448.2349. PMID 10600747.

[14] Agrawal RK, Sharma MR, Kiel MC, et al. (June 2004). "Visualization of ribosome-recycling factor on the Escherichia coli 70S ribosome: functional implications". Proc. Natl. Acad. Sci. U.S.A. 101 (24): 8900–8905. Bibcode:2004PNAS..101.8900A. doi:10.1073/pnas.0401904101. PMC 428444. PMID 15178758.

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