RG/RGG motif

The '''arginine-glycine''' or '''arginine-glycine-glycine''' ('''RG/RGG''') motif is a repeating amino acid sequence motif commonly found in RNA-binding proteins (RBPs). RGG regions in proteins are defined as two or more RG/RGG sequences within a stretch of 30 amino acids.<ref>{{cite journal |last1=Chowdhury |title=The RGG motif proteins: Interactions, functions, and regulations |journal=WIREs RNA |date=2023 |volume=14|issue=1 |article-number=e1748 |doi=10.1002/wrna.1748 |pmid=35661420 |pmc=9718894 }}</ref> Initially named the '''RGG box''', it confers a protein with the ability to bind double-stranded mRNA molecules.<ref>{{cite journal |last1=Kiledjian |title=Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box |journal=EMBO J |date=1992 |volume=11 |issue=7 |pages=2655–2664|doi=10.1002/j.1460-2075.1992.tb05331.x |pmid=1628625 |pmc=556741 }}</ref> The RGG motif has been observed in proteins from at least 12 animal species, including humans.<ref>{{cite journal |last1=Qian |title=Synthetic protein condensates for cellular and metabolic engineering |journal=Nat. Chem. Biol. |date=2022 |volume=18 |issue=12 |pages=1330–1340|doi=10.1038/s41589-022-01203-3 |pmid=36400990 }}</ref>

== Biochemical function== RGG motifs are primarily involved in mediating protein-RNA interactions. Positive charges from arginine residues promote electrostatic interactions with mRNA molecules. The composition and structure of the arginine side chain may also allow for specific interactions with other molecules as opposed to the other positively charged amino acids, lysine and histidine.<ref>{{cite journal |last1=Takahama |title=Identification of Ewing's sarcoma protein as a G-quadruplex DNA- and RNA-binding protein |journal=FEBS J. |date=2011 |volume=278 |issue=6 |pages=988–998|doi=10.1111/j.1742-4658.2011.08020.x |pmid=21244633 }}</ref> Glycine residues add flexibility to the peptide structure and promote their tendency to form intrinsically disordered regions. The RGG motif can also drive liquid-lipid phase separation of proteins inside cells as well as ''in vitro.''<ref>{{cite journal |last1=Qian |title=Synthetic protein condensates for cellular and metabolic engineering |journal=Nat. Chem. Biol. |date=2022 |volume=18 |issue=12 |pages=1330–1340|doi=10.1038/s41589-022-01203-3 |pmid=36400990 }}</ref><ref>{{cite bioRxiv |last1=Robinson |title=Cell-Free Expressed Membraneless Organelles Sequester RNA in Synthetic Cells |date=2023 |biorxiv=10.1101/2023.04.03.535479 }}</ref>

== Synthetic uses== Researchers have pursued creating condensates with novel functions for use in cellular and metabolic engineering. Synthetically designed proteins containing repeating RGG motifs have been used to form droplets with tunable properties in cells and ''in vitro.''<ref>{{cite journal |last1=Schuster |title=Controllable protein phase separation and modular recruitment to form responsive membraneless organelles |journal=Nat Commun |date=2018 |volume=9 |issue=1 |article-number=2985|doi=10.1038/s41467-018-05403-1 |pmid=30061688 |pmc=6065366 |bibcode=2018NatCo...9.2985S }}</ref><ref>{{cite journal |last1=Dai |title=Engineering synthetic biomolecular condensates. |journal=Nat Rev Bioeng |date=2023 |volume=1 |issue=7 |pages=466–480|doi=10.1038/s44222-023-00052-6 |pmid=37359769 |pmc=10107566 }}</ref>

== Notable RGG-containing proteins== RGG motif-containing proteins are the second most abundant group of RBPs in the human genome.<ref>{{cite journal |last1=Ozdilek |title=Intrinsically disordered RGG/RG domains mediate degenerate specificity in RNA binding |journal=Nucleic Acids Res. |date=2017 |volume=45 |issue=13 |pages=7984–7996|doi=10.1093/nar/gkx460 |pmid=28575444 |pmc=5570134 }}</ref><ref>{{cite journal |last1=Hentze |title=A brave new world of RNA-binding proteins |journal=Nat. Rev. Mol. Cell Biol. |date=2018 |volume=19 |issue=5 |pages=327–341|doi=10.1038/nrm.2017.130 |pmid=29339797 |bibcode=2018NRMCB..19..327H |url=https://eprints.gla.ac.uk/219002/1/219002.pdf }}</ref> They are involved in various RNA metabolism, export, and translation functions.

* Sbp1<ref>{{cite journal |last1=Jong |title=Saccharomyces cerevisiae SSB1 protein and its relationship to nucleolar RNA-binding protein |journal=Mol. Cell. Biol. |date=1987 |volume=19 |pages=2947–2955}}</ref> * Npl3<ref>{{cite journal |last1=Bossie |title=A mutant nuclear protein with similarity to RNA binding proteins interferes with nuclear import in yeast |journal=Mol. Biol. Cell |date=1992 |volume=3 |issue=8 |pages=875–893|doi=10.1091/mbc.3.8.875 |pmid=1392078 |pmc=275646 }}</ref><ref>{{cite journal |last1=Flach |title=A yeast RNA-binding protein shuttles between the nucleus and the cytoplasm |journal=Mol. Cell. Biol. |date=1994 |volume=14 |issue=12 |pages=8399–8407|doi=10.1128/mcb.14.12.8399-8407.1994 |pmid=7969175 |pmc=359379 }}</ref> * Ded1<ref>{{cite journal |last1=Iost |title=Ded1p, a DEAD-box protein required for translation initiation in Saccharomyces cerevisiae, is an RNA helicase |journal=J. Biol. Chem. |date=1999 |volume=274 |issue=25 |pages=17677–17683|doi=10.1074/jbc.274.25.17677 |doi-access=free |pmid=10364207 }}</ref> * FMR1<ref>{{cite journal |last1=Ashley |title=FMR1 protein: conserved RNP family domains and selective RNA binding. |journal=Science |date=1993 |volume=263 |issue=5133 |pages=563–566|doi=10.1126/science.7692601 |pmid=7692601 |bibcode=1993Sci...262..563A }}</ref> * FUS<ref>{{cite journal |last1=Crozat |title=Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma|journal=Nature |date=1993 |volume=363 |issue=6430 |pages=640–644|doi=10.1038/363640a0 |pmid=8510758 |bibcode=1993Natur.363..640C }}</ref><ref>{{cite journal |last1=Baechtold |title=Human 75-kDa DNA-pairing protein is identical to the pro-oncoprotein TLS/FUS and is able to promote D-loop formation |journal=J. Biol. Chem. |date=1999 |volume=274 |issue=48 |pages=34337–34342|doi=10.1074/jbc.274.48.34337 |doi-access=free |pmid=10567410 }}</ref> * Laf-1<ref>{{cite journal |last1=Elbaum-Garfinkle |title=The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics. |journal=Proc. Natl. Acad. Sci. |date=2015 |volume=112 |issue=23 |pages=7189–7194|doi=10.1073/pnas.1504822112 |doi-access=free |pmid=26015579 |pmc=4466716 |bibcode=2015PNAS..112.7189E }}</ref>

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Category:Bioinformatics