Optoribogenetic Control of Regulatory RNA Molecules

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Sep 25

PMID 32973178

Citations 10

Authors

Sebastian Pilsl

Charles Morgan

Moujab Choukeife

Andreas Moglich

Gunter Mayer

Affiliations

Soon will be listed here.

Abstract

Short regulatory RNA molecules underpin gene expression and govern cellular state and physiology. To establish an alternative layer of control over these processes, we generated chimeric regulatory RNAs that interact reversibly and light-dependently with the light-oxygen-voltage photoreceptor PAL. By harnessing this interaction, the function of micro RNAs (miRs) and short hairpin (sh) RNAs in mammalian cells can be regulated in a spatiotemporally precise manner. The underlying strategy is generic and can be adapted to near-arbitrary target sequences. Owing to full genetic encodability, it establishes optoribogenetic control of cell state and physiology. The method stands to facilitate the non-invasive, reversible and spatiotemporally resolved study of regulatory RNAs and protein function in cellular and organismal environments.

Citing Articles

Optogenetic Tools for Regulating RNA Metabolism and Functions.

Zheng R, Xue Z, You M Chembiochem. 2024; 25(24):e202400615.

PMID: 39316432 PMC: 11666399. DOI: 10.1002/cbic.202400615.

Regulatory RNAs: role as scaffolds assembling protein complexes and their epigenetic deregulation.

Poltronieri P Explor Target Antitumor Ther. 2024; 5(4):841-876.

PMID: 39280246 PMC: 11390297. DOI: 10.37349/etat.2024.00252.

Induction of bacterial expression at the mRNA level by light.

Ranzani A, Buchholz K, Blackholm M, Kopkin H, Moglich A Nucleic Acids Res. 2024; 52(16):10017-10028.

PMID: 39126322 PMC: 11381354. DOI: 10.1093/nar/gkae678.

An RNA Motif That Enables Optozyme Control and Light-Dependent Gene Expression in Bacteria and Mammalian Cells.

Pietruschka G, Ranzani A, Weber A, Patwari T, Pilsl S, Renzl C Adv Sci (Weinh). 2024; 11(12):e2304519.

PMID: 38227373 PMC: 10966536. DOI: 10.1002/advs.202304519.

Optogenetics meets physiology.

Ohnemus S, Vierock J, Schneider-Warme F Pflugers Arch. 2023; 475(12):1369-1373.

PMID: 38047968 PMC: 10730680. DOI: 10.1007/s00424-023-02887-9.

References

Meister G, Tuschl T . Mechanisms of gene silencing by double-stranded RNA. Nature. 2004; 431(7006):343-9. DOI: 10.1038/nature02873. View

Zamore P, Tuschl T, Sharp P, Bartel D . RNAi: double-stranded RNA directs the ATP-dependent cleavage of mRNA at 21 to 23 nucleotide intervals. Cell. 2000; 101(1):25-33. DOI: 10.1016/S0092-8674(00)80620-0. View

Hannon G . RNA interference. Nature. 2002; 418(6894):244-51. DOI: 10.1038/418244a. View

Sambandan S, Akbalik G, Kochen L, Rinne J, Kahlstatt J, Glock C . Activity-dependent spatially localized miRNA maturation in neuronal dendrites. Science. 2017; 355(6325):634-637. DOI: 10.1126/science.aaf8995. View

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

Werstuck G, Green M . Controlling gene expression in living cells through small molecule-RNA interactions. Science. 1998; 282(5387):296-8. DOI: 10.1126/science.282.5387.296. View

Boussebayle A, Torka D, Ollivaud S, Braun J, Bofill-Bosch C, Dombrowski M . Next-level riboswitch development-implementation of Capture-SELEX facilitates identification of a new synthetic riboswitch. Nucleic Acids Res. 2019; 47(9):4883-4895. PMC: 6511860. DOI: 10.1093/nar/gkz216. View

Topp S, Gallivan J . Emerging applications of riboswitches in chemical biology. ACS Chem Biol. 2010; 5(1):139-48. PMC: 2811087. DOI: 10.1021/cb900278x. View

Yen L, Svendsen J, Lee J, Gray J, Magnier M, Baba T . Exogenous control of mammalian gene expression through modulation of RNA self-cleavage. Nature. 2004; 431(7007):471-6. DOI: 10.1038/nature02844. View

10.

Mello C, Conte Jr D . Revealing the world of RNA interference. Nature. 2004; 431(7006):338-42. DOI: 10.1038/nature02872. View

11.

Dorsett Y, Tuschl T . siRNAs: applications in functional genomics and potential as therapeutics. Nat Rev Drug Discov. 2004; 3(4):318-29. DOI: 10.1038/nrd1345. View

12.

Kirkbride R, Lu J, Zhang C, Mosher R, Baulcombe D, Chen Z . Maternal small RNAs mediate spatial-temporal regulation of gene expression, imprinting, and seed development in . Proc Natl Acad Sci U S A. 2019; 116(7):2761-2766. PMC: 6377484. DOI: 10.1073/pnas.1807621116. View

13.

Bayer T, Smolke C . Programmable ligand-controlled riboregulators of eukaryotic gene expression. Nat Biotechnol. 2005; 23(3):337-43. DOI: 10.1038/nbt1069. View

14.

Szulc J, Wiznerowicz M, Sauvain M, Trono D, Aebischer P . A versatile tool for conditional gene expression and knockdown. Nat Methods. 2006; 3(2):109-16. DOI: 10.1038/nmeth846. View

15.

Berger S, Pesold B, Reber S, Schonig K, Berger A, Weidenfeld I . Quantitative analysis of conditional gene inactivation using rationally designed, tetracycline-controlled miRNAs. Nucleic Acids Res. 2010; 38(17):e168. PMC: 2943624. DOI: 10.1093/nar/gkq616. View

16.

Kumar D, An C, Yokobayashi Y . Conditional RNA interference mediated by allosteric ribozyme. J Am Chem Soc. 2009; 131(39):13906-7. DOI: 10.1021/ja905596t. View

17.

Atanasov J, Groher F, Weigand J, Suess B . Design and implementation of a synthetic pre-miR switch for controlling miRNA biogenesis in mammals. Nucleic Acids Res. 2017; 45(22):e181. PMC: 5727447. DOI: 10.1093/nar/gkx858. View

18.

Auslander D, Wieland M, Auslander S, Tigges M, Fussenegger M . Rational design of a small molecule-responsive intramer controlling transgene expression in mammalian cells. Nucleic Acids Res. 2011; 39(22):e155. PMC: 3239198. DOI: 10.1093/nar/gkr829. View

19.

Ebert M, Neilson J, Sharp P . MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods. 2007; 4(9):721-6. PMC: 3857099. DOI: 10.1038/nmeth1079. View

20.

Fulga T, McNeill E, Binari R, Yelick J, Blanche A, Booker M . A transgenic resource for conditional competitive inhibition of conserved Drosophila microRNAs. Nat Commun. 2015; 6:7279. PMC: 4471878. DOI: 10.1038/ncomms8279. View