Ribosome recycling factor

The ribosome recycling factor was discovered in the early 1970s by the work of Akira Kaji and Akikazu Hiroshima at the University of Pennsylvania.{{cite journal |vauthors=Hirashima A, Kaji A |title=Factor dependent breakdown of polysomes |journal=Biochem. Biophys. Res. Commun. |volume=41 |issue=4 |pages=877–883 |date=November 1970 |pmid=4920474 |doi=10.1016/0006-291X(70)90165-8}}{{cite journal |vauthors=Hirashima A, Kaji A |title=Factor-dependent release of ribosomes from messenger RNA. Requirement for two heat-stable factors |journal=J. Mol. Biol. |volume=65 |issue=1 |pages=43–58 |date=March 1972 |pmid=4553259 |doi=10.1016/0022-2836(72)90490-1}}{{cite journal |vauthors=Hirashima A, Kaji A |title=Purification and properties of ribosome-releasing factor |journal=Biochemistry |volume=11 |issue=22 |pages=4037–4044 |date=October 1972 |pmid=4563926 |doi=10.1021/bi00772a005 }}{{cite journal |vauthors=Hirashima A, Kaji A |title=Role of elongation factor G and a protein factor on the release of ribosomes from messenger ribonucleic acid |journal=J. Biol. Chem. |volume=248 |issue=21 |pages=7580–7587 |date=November 1973 |doi=10.1016/S0021-9258(19)43330-9 |pmid=4583357 |url=http://www.jbc.org/cgi/pmidlookup?view=long&pmid=4583357|doi-access=free }} 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.

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).{{cite journal |vauthors=Hirokawa G, Demeshkina N, Iwakura N, Kaji H, Kaji A |title=The ribosome-recycling step: Consensus or controversy? |journal=Trends Biochem. Sci. |volume=31 |issue=3 |pages=143–149 |date=March 2006 |pmid=16487710 |doi=10.1016/j.tibs.2006.01.007 |url=https://jdc.jefferson.edu/cgi/viewcontent.cgi?article=1005&context=bmpfp |url-access=subscription }} Depending on the tRNA, IF1–IF3 may also perform recycling.{{cite journal |last1=Pavlov |first1=MY |last2=Antoun |first2=A |last3=Lovmar |first3=M |last4=Ehrenberg |first4=M |title=Complementary roles of initiation factor 1 and ribosome recycling factor in 70S ribosome splitting. |journal=The EMBO Journal |date=18 June 2008 |volume=27 |issue=12 |pages=1706–17 |doi=10.1038/emboj.2008.99 |pmid=18497739 |pmc=2435134}}

• In Bacteria (specifically Escherichia coli), loss of the gene encoding RRF is deleterious.{{cite journal |vauthors=Janosi L, Shimizu I, Kaji A |title=Ribosome recycling factor (ribosome releasing factor) is essential for bacterial growth |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=91 |issue=10 |pages=4249–4253 |date=May 1994 |pmid=8183897 |pmc=43762 |doi=10.1073/pnas.91.10.4249|bibcode=1994PNAS...91.4249J |doi-access=free }} 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.{{cite journal |vauthors=Teyssier E, Hirokawa G, Tretiakova A, Jameson B, Kaji A, Kaji H |title=Temperature-sensitive mutation in yeast mitochondrial ribosome recycling factor (RRF) |journal=Nucleic Acids Res. |volume=31 |issue=14 |pages=4218–4226 |date=July 2003 |pmid=12853640 |pmc=165964 |url=|doi=10.1093/nar/gkg449}}

The crystal structure of RRF was first determined by X-ray diffraction in 1999.{{cite journal |vauthors=Selmer M, Al-Karadaghi S, Hirokawa G, Kaji A, Liljas A |title=Crystal structure of Thermotoga maritima ribosome recycling factor: a tRNA mimic |journal=Science |volume=286 |issue=5448 |pages=2349–2352 |date=December 1999 |pmid=10600747 |doi=10.1126/science.286.5448.2349}} 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 [http://www.pharm.kyoto-u.ac.jp/structbl/gallery/structure/rrf.jpg here].

Despite the tRNA-mimicry, RRF binds to ribosomes quite differently from the way tRNA does.{{cite journal |vauthors=Agrawal RK, Sharma MR, Kiel MC, etal |title=Visualization of ribosome-recycling factor on the Escherichia coli 70S ribosome: functional implications |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue=24 |pages=8900–8905 |date=June 2004 |pmid=15178758 |pmc=428444 |doi=10.1073/pnas.0401904101 |bibcode=2004PNAS..101.8900A |doi-access=free }} 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.

• Ribosome
• Translation (genetics)
• Eukaryotic release factors

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• {{MeshName|ribosome+releasing+factor}}
• {{cite journal |last=Bao |first=Letian |title=Rate-limiting hydrolysis in ribosomal release reactions revealed by ester activation |journal=Journal of Biological Chemistry |date=2022-11-01 |volume=298 |issue=11 |page=102509 |doi=10.1016/j.jbc.2022.102509 }}

Category:Proteins