Synthetic Translational Regulation by an L7Ae-kink-turn RNP Switch

Overview

Journal Nat Chem Biol

Specialties Biochemistry
Biology
Chemistry

Date 2009 Dec 18

PMID 20016495

Citations 67

Authors

Hirohide Saito

Tetsuhiro Kobayashi

Tomoaki Hara

Yoshihiko Fujita

Karin Hayashi

Rie Furushima

Tan Inoue

Affiliations

Soon will be listed here.

Abstract

The regulation of cell signaling pathways and the reconstruction of genetic circuits are important aspects of bioengineering research. Both of these goals require molecular devices to transmit information from an input biomacromolecule to the desired outputs. Here, we show that an RNA-protein (RNP)-containing L7Ae-kink-turn interaction can be used to construct translational regulators under control of an input protein that regulates the expression of desired output proteins. We built a system in which L7Ae, an archaeal ribosomal protein, regulates the translation of a designed mRNA in vitro and in human cells. The translational regulator composed of the RNP might provide new therapeutic strategies based on the detection, repair or rewiring of intrinsic cellular defects, and it may also serve as an invaluable tool for the dissection of the behavior of complex, higher-order circuits in the cell.

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References

Purnick P, Weiss R . The second wave of synthetic biology: from modules to systems. Nat Rev Mol Cell Biol. 2009; 10(6):410-22. DOI: 10.1038/nrm2698. View

Win M, Smolke C . Higher-order cellular information processing with synthetic RNA devices. Science. 2008; 322(5900):456-60. PMC: 2805114. DOI: 10.1126/science.1160311. View

Gebauer F, Hentze M . Molecular mechanisms of translational control. Nat Rev Mol Cell Biol. 2004; 5(10):827-35. PMC: 7097087. DOI: 10.1038/nrm1488. View

Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View

Sharma V, Nomura Y, Yokobayashi Y . Engineering complex riboswitch regulation by dual genetic selection. J Am Chem Soc. 2008; 130(48):16310-5. DOI: 10.1021/ja805203w. View

Ogawa A, Maeda M . An artificial aptazyme-based riboswitch and its cascading system in E. coli. Chembiochem. 2007; 9(2):206-9. DOI: 10.1002/cbic.200700478. View

Gottesman S . The small RNA regulators of Escherichia coli: roles and mechanisms*. Annu Rev Microbiol. 2004; 58:303-28. DOI: 10.1146/annurev.micro.58.030603.123841. View

Yamauchi T, Miyoshi D, Kubodera T, Ban M, Nishimura A, Sugimoto N . Riboswitches for enhancing target gene expression in eukaryotes. Chembiochem. 2008; 9(7):1040-3. DOI: 10.1002/cbic.200700782. View

Szostak J, Bartel D, Luisi P . Synthesizing life. Nature. 2001; 409(6818):387-90. DOI: 10.1038/35053176. View

10.

Macias S, Bragulat M, Tardiff D, Vilardell J . L30 binds the nascent RPL30 transcript to repress U2 snRNP recruitment. Mol Cell. 2008; 30(6):732-42. DOI: 10.1016/j.molcel.2008.05.002. View

11.

Reichow S, Hamma T, Ferre-DAmare A, Varani G . The structure and function of small nucleolar ribonucleoproteins. Nucleic Acids Res. 2007; 35(5):1452-64. PMC: 1865073. DOI: 10.1093/nar/gkl1172. View

12.

Ray P, Jia J, Yao P, Majumder M, Hatzoglou M, Fox P . A stress-responsive RNA switch regulates VEGFA expression. Nature. 2008; 457(7231):915-9. PMC: 2858559. DOI: 10.1038/nature07598. View

13.

Matsumura S, Ikawa Y, Inoue T . Biochemical characterization of the kink-turn RNA motif. Nucleic Acids Res. 2003; 31(19):5544-51. PMC: 206460. DOI: 10.1093/nar/gkg760. View

14.

Katoh T, Suzuki T . Specific residues at every third position of siRNA shape its efficient RNAi activity. Nucleic Acids Res. 2007; 35(4):e27. PMC: 1851635. DOI: 10.1093/nar/gkl1120. View

15.

Chavatte L, Brown B, Driscoll D . Ribosomal protein L30 is a component of the UGA-selenocysteine recoding machinery in eukaryotes. Nat Struct Mol Biol. 2005; 12(5):408-16. DOI: 10.1038/nsmb922. View

16.

Hamma T, Ferre-DAmare A . Structure of protein L7Ae bound to a K-turn derived from an archaeal box H/ACA sRNA at 1.8 A resolution. Structure. 2004; 12(5):893-903. DOI: 10.1016/j.str.2004.03.015. View

17.

Wieland M, Hartig J . Improved aptazyme design and in vivo screening enable riboswitching in bacteria. Angew Chem Int Ed Engl. 2008; 47(14):2604-7. DOI: 10.1002/anie.200703700. View

18.

Win M, Liang J, Smolke C . Frameworks for programming biological function through RNA parts and devices. Chem Biol. 2009; 16(3):298-310. PMC: 2713350. DOI: 10.1016/j.chembiol.2009.02.011. View

19.

Turner B, Melcher S, Wilson T, Norman D, Lilley D . Induced fit of RNA on binding the L7Ae protein to the kink-turn motif. RNA. 2005; 11(8):1192-200. PMC: 1370803. DOI: 10.1261/rna.2680605. View

20.

Paraskeva E, Atzberger A, Hentze M . A translational repression assay procedure (TRAP) for RNA-protein interactions in vivo. Proc Natl Acad Sci U S A. 1998; 95(3):951-6. PMC: 18636. DOI: 10.1073/pnas.95.3.951. View