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.[1] Initially named the RGG box, it confers a protein with the ability to bind double-stranded mRNA molecules.[2] The RGG motif has been observed in proteins from at least 12 animal species, including humans.[3]
Biochemical function
[edit]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.[4] 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.[5][6]
Synthetic uses
[edit]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.[7][8]
Notable RGG-containing proteins
[edit]RGG motif-containing proteins are the second most abundant group of RBPs in the human genome.[9][10] They are involved in various RNA metabolism, export, and translation functions.
References
[edit]- ^ Chowdhury (2023). "The RGG motif proteins: Interactions, functions, and regulations". WIREs RNA. 14 (1): e1748. doi:10.1002/wrna.1748. PMC 9718894. PMID 35661420.
- ^ Kiledjian (1992). "Primary structure and binding activity of the hnRNP U protein: binding RNA through RGG box". EMBO J. 11 (7): 2655–2664. doi:10.1002/j.1460-2075.1992.tb05331.x. PMC 556741. PMID 1628625.
- ^ Qian (2022). "Synthetic protein condensates for cellular and metabolic engineering". Nat. Chem. Biol. 18 (12): 1330–1340. doi:10.1038/s41589-022-01203-3. PMID 36400990.
- ^ Takahama (2011). "Identification of Ewing's sarcoma protein as a G-quadruplex DNA- and RNA-binding protein". FEBS J. 278 (6): 988–998. doi:10.1111/j.1742-4658.2011.08020.x. PMID 21244633.
- ^ Qian (2022). "Synthetic protein condensates for cellular and metabolic engineering". Nat. Chem. Biol. 18 (12): 1330–1340. doi:10.1038/s41589-022-01203-3. PMID 36400990.
- ^ Robinson (2023). "Cell-Free Expressed Membraneless Organelles Sequester RNA in Synthetic Cells". bioRxiv. doi:10.1101/2023.04.03.535479. PMC 10104018. PMID 37066403.
- ^ Schuster (2018). "Controllable protein phase separation and modular recruitment to form responsive membraneless organelles". Nat Commun. 9 (1): 2985. Bibcode:2018NatCo...9.2985S. doi:10.1038/s41467-018-05403-1. PMC 6065366. PMID 30061688.
- ^ Dai (2023). "Engineering synthetic biomolecular condensates". Nat Rev Bioeng. 1 (7): 466–480. doi:10.1038/s44222-023-00052-6. PMC 10107566. PMID 37359769.
- ^ Ozdilek (2017). "Intrinsically disordered RGG/RG domains mediate degenerate specificity in RNA binding". Nucleic Acids Res. 45 (13): 7984–7996. doi:10.1093/nar/gkx460. PMC 5570134. PMID 28575444.
- ^ Hentze (2018). "A brave new world of RNA-binding proteins" (PDF). Nat. Rev. Mol. Cell Biol. 19 (5): 327–341. doi:10.1038/nrm.2017.130. PMID 29339797.
- ^ Jong (1987). "Saccharomyces cerevisiae SSB1 protein and its relationship to nucleolar RNA-binding protein". Mol. Cell. Biol. 19: 2947–2955.
- ^ Bossie (1992). "A mutant nuclear protein with similarity to RNA binding proteins interferes with nuclear import in yeast". Mol. Biol. Cell. 3 (8): 875–893. doi:10.1091/mbc.3.8.875. PMC 275646. PMID 1392078.
- ^ Flach (1994). "A yeast RNA-binding protein shuttles between the nucleus and the cytoplasm". Mol. Cell. Biol. 14 (12): 8399–8407. doi:10.1128/mcb.14.12.8399-8407.1994. PMC 359379. PMID 7969175.
- ^ Iost (1999). "Ded1p, a DEAD-box protein required for translation initiation in Saccharomyces cerevisiae, is an RNA helicase". J. Biol. Chem. 274 (25): 17677–17683. doi:10.1074/jbc.274.25.17677. PMID 10364207.
- ^ Ashley (1993). "FMR1 protein: conserved RNP family domains and selective RNA binding". Science. 263 (5133): 563–566. Bibcode:1993Sci...262..563A. doi:10.1126/science.7692601. PMID 7692601.
- ^ Crozat (1993). "Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma". Nature. 363 (6430): 640–644. Bibcode:1993Natur.363..640C. doi:10.1038/363640a0. PMID 8510758.
- ^ Baechtold (1999). "Human 75-kDa DNA-pairing protein is identical to the pro-oncoprotein TLS/FUS and is able to promote D-loop formation". J. Biol. Chem. 274 (48): 34337–34342. doi:10.1074/jbc.274.48.34337. PMID 10567410.
- ^ Elbaum-Garfinkle (2015). "The disordered P granule protein LAF-1 drives phase separation into droplets with tunable viscosity and dynamics". Proc. Natl. Acad. Sci. 112 (23): 7189–7194. Bibcode:2015PNAS..112.7189E. doi:10.1073/pnas.1504822112. PMC 4466716. PMID 26015579.