Translational Machinery Condones Polyadenosine Repeats

Overview

Journal Elife

Specialty Biology

Date 2020 May 30

PMID 32469313

Citations 11

Authors

Slavica Pavlovic Djuranovic

Jessey Erath

Ryan J Andrews

Peter O Bayguinov

Joyce J Chung

Douglas L Chalker

James Aj Fitzpatrick

Walter N Moss

Pawel Szczesny

Sergej Djuranovic

Affiliations

Soon will be listed here.

Abstract

is a causative agent of human malaria. Sixty percent of mRNAs from its extremely AT-rich (81%) genome harbor long polyadenosine (polyA) runs within their ORFs, distinguishing the parasite from its hosts and other sequenced organisms. Recent studies indicate polyA runs cause ribosome stalling and frameshifting, triggering mRNA surveillance pathways and attenuating protein synthesis. Here, we show that is an exception to this rule. We demonstrate that both endogenous genes and reporter sequences containing long polyA runs are efficiently and accurately translated in cells. We show that polyA runs do not elicit any response from No Go Decay (NGD) or result in the production of frameshifted proteins. This is in stark contrast to what we observe in human cells or , an organism with similar AT-content. Finally, using stalling reporters we show that cells evolved not to have a fully functional NGD pathway.

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References

Lacsina J, LaMonte G, Nicchitta C, Chi J . Polysome profiling of the malaria parasite Plasmodium falciparum. Mol Biochem Parasitol. 2011; 179(1):42-6. PMC: 3135974. DOI: 10.1016/j.molbiopara.2011.05.003. View

Faure G, Ogurtsov A, Shabalina S, Koonin E . Role of mRNA structure in the control of protein folding. Nucleic Acids Res. 2016; 44(22):10898-10911. PMC: 5159526. DOI: 10.1093/nar/gkw671. View

Zhang M, Wang C, Otto T, Oberstaller J, Liao X, Adapa S . Uncovering the essential genes of the human malaria parasite by saturation mutagenesis. Science. 2018; 360(6388). PMC: 6360947. DOI: 10.1126/science.aap7847. View

Trager W, Jensen J . Human malaria parasites in continuous culture. 1976. J Parasitol. 2005; 91(3):484-6. DOI: 10.1645/0022-3395(2005)091[0484:HMPICC]2.0.CO;2. View

Szadeczky-Kardoss I, Gal L, Auber A, Taller J, Silhavy D . The No-go decay system degrades plant mRNAs that contain a long A-stretch in the coding region. Plant Sci. 2018; 275:19-27. DOI: 10.1016/j.plantsci.2018.07.008. View

Saul A, Battistutta D . Codon usage in Plasmodium falciparum. Mol Biochem Parasitol. 1988; 27(1):35-42. DOI: 10.1016/0166-6851(88)90022-9. View

Guydosh N, Green R . Translation of poly(A) tails leads to precise mRNA cleavage. RNA. 2017; 23(5):749-761. PMC: 5393183. DOI: 10.1261/rna.060418.116. View

Mouzakis K, Lang A, Vander Meulen K, Easterday P, Butcher S . HIV-1 frameshift efficiency is primarily determined by the stability of base pairs positioned at the mRNA entrance channel of the ribosome. Nucleic Acids Res. 2012; 41(3):1901-13. PMC: 3561942. DOI: 10.1093/nar/gks1254. View

Kobayashi K, Takano R, Takemae H, Sugi T, Ishiwa A, Gong H . Analyses of interactions between heparin and the apical surface proteins of Plasmodium falciparum. Sci Rep. 2013; 3:3178. PMC: 3822384. DOI: 10.1038/srep03178. View

10.

Szafranski K, Lehmann R, Parra G, Guigo R, Glockner G . Gene organization features in A/T-rich organisms. J Mol Evol. 2005; 60(1):90-8. DOI: 10.1007/s00239-004-0201-2. View

11.

Hudson B, Zaher H . O6-Methylguanosine leads to position-dependent effects on ribosome speed and fidelity. RNA. 2015; 21(9):1648-59. PMC: 4536324. DOI: 10.1261/rna.052464.115. View

12.

Lorenz R, Bernhart S, Honer Zu Siederdissen C, Tafer H, Flamm C, Stadler P . ViennaRNA Package 2.0. Algorithms Mol Biol. 2011; 6:26. PMC: 3319429. DOI: 10.1186/1748-7188-6-26. View

13.

Koutmou K, Schuller A, Brunelle J, Radhakrishnan A, Djuranovic S, Green R . Ribosomes slide on lysine-encoding homopolymeric A stretches. Elife. 2015; 4. PMC: 4363877. DOI: 10.7554/eLife.05534. View

14.

Lu J, Deutsch C . Electrostatics in the ribosomal tunnel modulate chain elongation rates. J Mol Biol. 2008; 384(1):73-86. PMC: 2655213. DOI: 10.1016/j.jmb.2008.08.089. View

15.

Romero L, Nguyen T, Deville B, Ogunjumo O, James A . The MB2 gene family of Plasmodium species has a unique combination of S1 and GTP-binding domains. BMC Bioinformatics. 2004; 5:83. PMC: 482805. DOI: 10.1186/1471-2105-5-83. View

16.

Kim H, Liu F, Fei J, Bustamante C, Gonzalez Jr R, Tinoco Jr I . A frameshifting stimulatory stem loop destabilizes the hybrid state and impedes ribosomal translocation. Proc Natl Acad Sci U S A. 2014; 111(15):5538-43. PMC: 3992627. DOI: 10.1073/pnas.1403457111. View

17.

Petrone P, Snow C, Lucent D, Pande V . Side-chain recognition and gating in the ribosome exit tunnel. Proc Natl Acad Sci U S A. 2008; 105(43):16549-54. PMC: 2575457. DOI: 10.1073/pnas.0801795105. View

18.

Zur H, Tuller T . Strong association between mRNA folding strength and protein abundance in S. cerevisiae. EMBO Rep. 2012; 13(3):272-7. PMC: 3323128. DOI: 10.1038/embor.2011.262. View

19.

Juszkiewicz S, Hegde R . Initiation of Quality Control during Poly(A) Translation Requires Site-Specific Ribosome Ubiquitination. Mol Cell. 2017; 65(4):743-750.e4. PMC: 5316413. DOI: 10.1016/j.molcel.2016.11.039. View

20.

Darnell A, Subramaniam A, OShea E . Translational Control through Differential Ribosome Pausing during Amino Acid Limitation in Mammalian Cells. Mol Cell. 2018; 71(2):229-243.e11. PMC: 6516488. DOI: 10.1016/j.molcel.2018.06.041. View