Concerted Expression of a Cell Cycle Regulator and a Metabolic Enzyme from a Bicistronic Transcript in Plants

Overview

Journal Nat Plants

Specialties Biology
Genetics

Date 2019 Feb 10

PMID 30737513

Citations 14

Authors

Laura Lorenzo-Orts

Janika Witthoeft

Jules Deforges

Jacobo Martinez

Sylvain Loubery

Aleksandra Placzek

Yves Poirier

Ludwig A Hothorn

Yvon Jaillais

Michael Hothorn

Affiliations

Soon will be listed here.

Abstract

Eukaryotic mRNAs frequently contain upstream open reading frames (uORFs), encoding small peptides that may control translation of the main ORF (mORF). Here, we report the characterization of a distinct bicistronic transcript in Arabidopsis. We analysed loss-of-function phenotypes of the inorganic polyphosphatase TRIPHOSPHATE TUNNEL METALLOENZYME 3 (AtTTM3), and found that catalytically inactive versions of the enzyme could fully complement embryo and growth-related phenotypes. We could rationalize these puzzling findings by characterizing a uORF in the AtTTM3 locus encoding CELL DIVISION CYCLE PROTEIN 26 (CDC26), an orthologue of the cell cycle regulator. We demonstrate that AtCDC26 is part of the plant anaphase promoting complex/cyclosome (APC/C), regulates accumulation of APC/C target proteins and controls cell division, growth and embryo development. AtCDC26 and AtTTM3 are translated from a single transcript conserved across the plant lineage. While there is no apparent biochemical connection between the two gene products, AtTTM3 coordinates AtCDC26 translation by recruiting the transcript into polysomes. Our work highlights that uORFs may encode functional proteins in plant genomes.

Citing Articles

Leaky ribosomal scanning enables tunable translation of bicistronic ORFs in green algae.

Duenas M, Craig R, Gallaher S, Moseley J, Merchant S Proc Natl Acad Sci U S A. 2025; 122(9):e2417695122.

PMID: 40009642 PMC: 11892635. DOI: 10.1073/pnas.2417695122.

Leaky ribosomal scanning enables tunable translation of bicistronic ORFs in green algae.

Duenas M, Craig R, Gallaher S, Moseley J, Merchant S bioRxiv. 2024; .

PMID: 39091764 PMC: 11291117. DOI: 10.1101/2024.07.24.605010.

Spinach genomes reveal migration history and candidate genes for important crop traits.

Nguyen-Hoang A, Sandell F, Himmelbauer H, Dohm J NAR Genom Bioinform. 2024; 6(2):lqae034.

PMID: 38633427 PMC: 11023180. DOI: 10.1093/nargab/lqae034.

What, where, and how: Regulation of translation and the translational landscape in plants.

Wu H, Jen J, Hsu P Plant Cell. 2023; 36(5):1540-1564.

PMID: 37437121 PMC: 11062462. DOI: 10.1093/plcell/koad197.

Triphosphate Tunnel Metalloenzyme 2 Acts as a Downstream Factor of ABI4 in ABA-Mediated Seed Germination.

Feng Y, Li T, Wang S, Lu Y, Yuan T Int J Mol Sci. 2023; 24(10).

PMID: 37240339 PMC: 10218978. DOI: 10.3390/ijms24108994.

References

Oyama M, Itagaki C, Hata H, Suzuki Y, Izumi T, Natsume T . Analysis of small human proteins reveals the translation of upstream open reading frames of mRNAs. Genome Res. 2004; 14(10B):2048-52. PMC: 528919. DOI: 10.1101/gr.2384604. View

Johnstone T, Bazzini A, Giraldez A . Upstream ORFs are prevalent translational repressors in vertebrates. EMBO J. 2016; 35(7):706-23. PMC: 4818764. DOI: 10.15252/embj.201592759. View

Wethmar K . The regulatory potential of upstream open reading frames in eukaryotic gene expression. Wiley Interdiscip Rev RNA. 2014; 5(6):765-78. DOI: 10.1002/wrna.1245. View

Wethmar K, Barbosa-Silva A, Andrade-Navarro M, Leutz A . uORFdb--a comprehensive literature database on eukaryotic uORF biology. Nucleic Acids Res. 2013; 42(Database issue):D60-7. PMC: 3964959. DOI: 10.1093/nar/gkt952. View

Menschaert G, Van Criekinge W, Notelaers T, Koch A, Crappe J, Gevaert K . Deep proteome coverage based on ribosome profiling aids mass spectrometry-based protein and peptide discovery and provides evidence of alternative translation products and near-cognate translation initiation events. Mol Cell Proteomics. 2013; 12(7):1780-90. PMC: 3708165. DOI: 10.1074/mcp.M113.027540. View

Schepetilnikov M, Dimitrova M, Mancera-Martinez E, Geldreich A, Keller M, Ryabova L . TOR and S6K1 promote translation reinitiation of uORF-containing mRNAs via phosphorylation of eIF3h. EMBO J. 2013; 32(8):1087-102. PMC: 3630359. DOI: 10.1038/emboj.2013.61. View

Zhou F, Roy B, Dunlap J, Enganti R, von Arnim A . Translational control of Arabidopsis meristem stability and organogenesis by the eukaryotic translation factor eIF3h. PLoS One. 2014; 9(4):e95396. PMC: 3988188. DOI: 10.1371/journal.pone.0095396. View

Pajerowska-Mukhtar K, Wang W, Tada Y, Oka N, Tucker C, Fonseca J . The HSF-like transcription factor TBF1 is a major molecular switch for plant growth-to-defense transition. Curr Biol. 2012; 22(2):103-12. PMC: 3298764. DOI: 10.1016/j.cub.2011.12.015. View

Starck S, Tsai J, Chen K, Shodiya M, Wang L, Yahiro K . Translation from the 5' untranslated region shapes the integrated stress response. Science. 2016; 351(6272):aad3867. PMC: 4882168. DOI: 10.1126/science.aad3867. View

10.

Wiese A, Elzinga N, Wobbes B, Smeekens S . A conserved upstream open reading frame mediates sucrose-induced repression of translation. Plant Cell. 2004; 16(7):1717-29. PMC: 514156. DOI: 10.1105/tpc.019349. View

11.

Kurihara Y, Matsui A, Hanada K, Kawashima M, Ishida J, Morosawa T . Genome-wide suppression of aberrant mRNA-like noncoding RNAs by NMD in Arabidopsis. Proc Natl Acad Sci U S A. 2009; 106(7):2453-8. PMC: 2650177. DOI: 10.1073/pnas.0808902106. View

12.

Nyiko T, Sonkoly B, Merai Z, Benkovics A, Silhavy D . Plant upstream ORFs can trigger nonsense-mediated mRNA decay in a size-dependent manner. Plant Mol Biol. 2009; 71(4-5):367-78. DOI: 10.1007/s11103-009-9528-4. View

13.

Mouilleron H, Delcourt V, Roucou X . Death of a dogma: eukaryotic mRNAs can code for more than one protein. Nucleic Acids Res. 2015; 44(1):14-23. PMC: 4705651. DOI: 10.1093/nar/gkv1218. View

14.

Ryabova L, Pooggin M, Hohn T . Translation reinitiation and leaky scanning in plant viruses. Virus Res. 2005; 119(1):52-62. DOI: 10.1016/j.virusres.2005.10.017. View

15.

Lee S . Expression of growth/differentiation factor 1 in the nervous system: conservation of a bicistronic structure. Proc Natl Acad Sci U S A. 1991; 88(10):4250-4. PMC: 51636. DOI: 10.1073/pnas.88.10.4250. View

16.

Klemke M, Kehlenbach R, Huttner W . Two overlapping reading frames in a single exon encode interacting proteins--a novel way of gene usage. EMBO J. 2001; 20(14):3849-60. PMC: 125537. DOI: 10.1093/emboj/20.14.3849. View

17.

Lee C, Lai H, Lee Y, Chien C, Chern Y . The A2A adenosine receptor is a dual coding gene: a novel mechanism of gene usage and signal transduction. J Biol Chem. 2013; 289(3):1257-70. PMC: 3894312. DOI: 10.1074/jbc.M113.509059. View

18.

Autio K, Kastaniotis A, Pospiech H, Miinalainen I, Schonauer M, Dieckmann C . An ancient genetic link between vertebrate mitochondrial fatty acid synthesis and RNA processing. FASEB J. 2007; 22(2):569-78. DOI: 10.1096/fj.07-8986. View

19.

Moeder W, Garcia-Petit C, Ung H, Fucile G, Samuel M, Christendat D . Crystal structure and biochemical analyses reveal that the Arabidopsis triphosphate tunnel metalloenzyme AtTTM3 is a tripolyphosphatase involved in root development. Plant J. 2013; 76(4):615-26. DOI: 10.1111/tpj.12325. View

20.

Martinez J, Truffault V, Hothorn M . Structural Determinants for Substrate Binding and Catalysis in Triphosphate Tunnel Metalloenzymes. J Biol Chem. 2015; 290(38):23348-60. PMC: 4641920. DOI: 10.1074/jbc.M115.674473. View