Maturation of Selected Human Mitochondrial TRNAs Requires Deadenylation

Overview

Journal Elife

Specialty Biology

Date 2017 Jul 27

PMID 28745585

Citations 48

Authors

Sarah F Pearce

Joanna Rorbach

Lindsey Van Haute

Aaron R DSouza

Pedro Rebelo-Guiomar

Christopher A Powell

Ian Brierley

Andrew E Firth

Michal Minczuk

Affiliations

Soon will be listed here.

Abstract

Human mitochondria contain a genome (mtDNA) that encodes essential subunits of the oxidative phosphorylation system. Expression of mtDNA entails multi-step maturation of precursor RNA. In other systems, the RNA life cycle involves surveillance mechanisms, however, the details of RNA quality control have not been extensively characterised in human mitochondria. Using a mitochondrial ribosome profiling and mitochondrial poly(A)-tail RNA sequencing (MPAT-Seq) assay, we identify the poly(A)-specific exoribonuclease PDE12 as a major factor for the quality control of mitochondrial non-coding RNAs. The lack of PDE12 results in a spurious polyadenylation of the 3' ends of the mitochondrial (mt-) rRNA and mt-tRNA. While the aberrant adenylation of 16S mt-rRNA did not affect the integrity of the mitoribosome, spurious poly(A) additions to mt-tRNA led to reduced levels of aminoacylated pool of certain mt-tRNAs and mitoribosome stalling at the corresponding codons. Therefore, our data uncover a new, deadenylation-dependent mtRNA maturation pathway in human mitochondria.

Citing Articles

PDE12 mediated pruning of the poly-A tail of mitochondrial DNA-encoded tRNAs is essential for survival.

Yu C, Tigano M, Seifert E EMBO Mol Med. 2024; 17(1):3-5.

PMID: 39567836 PMC: 11730969. DOI: 10.1038/s44321-024-00171-6.

Pathogenic PDE12 variants impair mitochondrial RNA processing causing neonatal mitochondrial disease.

Van Haute L, Palenikova P, Tang J, Nash P, Simon M, Pyle A EMBO Mol Med. 2024; 17(1):193-210.

PMID: 39567835 PMC: 11729904. DOI: 10.1038/s44321-024-00172-5.

Unraveling the roles and mechanisms of mitochondrial translation in normal and malignant hematopoiesis.

Liu L, Shao M, Huang Y, Qian P, Huang H J Hematol Oncol. 2024; 17(1):95.

PMID: 39396039 PMC: 11470598. DOI: 10.1186/s13045-024-01615-9.

Mitochondrial RNA maturation.

Chrzanowska-Lightowlers Z, Lightowlers R RNA Biol. 2024; 21(1):28-39.

PMID: 39385590 PMC: 11469412. DOI: 10.1080/15476286.2024.2414157.

The human mitochondrial mRNA structurome reveals mechanisms of gene expression.

Moran J, Brivanlou A, Brischigliaro M, Fontanesi F, Rouskin S, Barrientos A Science. 2024; 385(6706):eadm9238.

PMID: 39024447 PMC: 11510358. DOI: 10.1126/science.adm9238.

References

Wood E, Bledsoe R, Chai J, Daka P, Deng H, Ding Y . The Role of Phosphodiesterase 12 (PDE12) as a Negative Regulator of the Innate Immune Response and the Discovery of Antiviral Inhibitors. J Biol Chem. 2015; 290(32):19681-96. PMC: 4528132. DOI: 10.1074/jbc.M115.653113. View

Gilkerson R, Schon E, Hernandez E, Davidson M . Mitochondrial nucleoids maintain genetic autonomy but allow for functional complementation. J Cell Biol. 2008; 181(7):1117-28. PMC: 2442202. DOI: 10.1083/jcb.200712101. View

Passmore L, Taatjes D . Macromolecular Complexes in Transcription and Co-Transcriptional RNA Processing. J Mol Biol. 2016; 428(12):2539-2541. DOI: 10.1016/j.jmb.2016.05.001. View

Liao Y, Smyth G, Shi W . The Subread aligner: fast, accurate and scalable read mapping by seed-and-vote. Nucleic Acids Res. 2013; 41(10):e108. PMC: 3664803. DOI: 10.1093/nar/gkt214. View

Langmead B, Salzberg S . Fast gapped-read alignment with Bowtie 2. Nat Methods. 2012; 9(4):357-9. PMC: 3322381. DOI: 10.1038/nmeth.1923. View

Temperley R, Seneca S, Tonska K, Bartnik E, Bindoff L, Lightowlers R . Investigation of a pathogenic mtDNA microdeletion reveals a translation-dependent deadenylation decay pathway in human mitochondria. Hum Mol Genet. 2003; 12(18):2341-8. DOI: 10.1093/hmg/ddg238. View

Ougland R, Zhang C, Liiv A, Johansen R, Seeberg E, Hou Y . AlkB restores the biological function of mRNA and tRNA inactivated by chemical methylation. Mol Cell. 2004; 16(1):107-16. DOI: 10.1016/j.molcel.2004.09.002. View

Reichert A, Rothbauer U, Morl M . Processing and editing of overlapping tRNAs in human mitochondria. J Biol Chem. 1998; 273(48):31977-84. DOI: 10.1074/jbc.273.48.31977. View

Powell C, Kopajtich R, DSouza A, Rorbach J, Kremer L, Husain R . TRMT5 Mutations Cause a Defect in Post-transcriptional Modification of Mitochondrial tRNA Associated with Multiple Respiratory-Chain Deficiencies. Am J Hum Genet. 2015; 97(2):319-28. PMC: 4573257. DOI: 10.1016/j.ajhg.2015.06.011. View

10.

Jackman J, Phizicky E . tRNAHis guanylyltransferase catalyzes a 3'-5' polymerization reaction that is distinct from G-1 addition. Proc Natl Acad Sci U S A. 2006; 103(23):8640-5. PMC: 1482633. DOI: 10.1073/pnas.0603068103. View

11.

Poulsen J, Andersen K, Kjaer K, Durand F, Faou P, Lindelov Vestergaard A . Human 2'-phosphodiesterase localizes to the mitochondrial matrix with a putative function in mitochondrial RNA turnover. Nucleic Acids Res. 2011; 39(9):3754-70. PMC: 3089451. DOI: 10.1093/nar/gkq1282. View

12.

Crosby A, Patel H, Chioza B, Proukakis C, Gurtz K, Patton M . Defective mitochondrial mRNA maturation is associated with spastic ataxia. Am J Hum Genet. 2010; 87(5):655-60. PMC: 2978972. DOI: 10.1016/j.ajhg.2010.09.013. View

13.

Karniely S, Weekes M, Antrobus R, Rorbach J, van Haute L, Umrania Y . Human Cytomegalovirus Infection Upregulates the Mitochondrial Transcription and Translation Machineries. mBio. 2016; 7(2):e00029. PMC: 4807356. DOI: 10.1128/mBio.00029-16. View

14.

Johnston M, Hearl W . Purification and characterization of a 2'-phosphodiesterase from bovine spleen. J Biol Chem. 1987; 262(17):8377-82. View

15.

Deutscher M . Degradation of RNA in bacteria: comparison of mRNA and stable RNA. Nucleic Acids Res. 2006; 34(2):659-66. PMC: 1360286. DOI: 10.1093/nar/gkj472. View

16.

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N . The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009; 25(16):2078-9. PMC: 2723002. DOI: 10.1093/bioinformatics/btp352. View

17.

Nandakumar J, Schwer B, Schaffrath R, Shuman S . RNA repair: an antidote to cytotoxic eukaryal RNA damage. Mol Cell. 2008; 31(2):278-86. PMC: 3289999. DOI: 10.1016/j.molcel.2008.05.019. View

18.

Rorbach J, Nicholls T, Minczuk M . PDE12 removes mitochondrial RNA poly(A) tails and controls translation in human mitochondria. Nucleic Acids Res. 2011; 39(17):7750-63. PMC: 3177208. DOI: 10.1093/nar/gkr470. View

19.

Rorbach J, Bobrowicz A, Pearce S, Minczuk M . Polyadenylation in bacteria and organelles. Methods Mol Biol. 2014; 1125:211-27. DOI: 10.1007/978-1-62703-971-0_18. View

20.

Van Haute L, Dietmann S, Kremer L, Hussain S, Pearce S, Powell C . Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3. Nat Commun. 2016; 7:12039. PMC: 4931328. DOI: 10.1038/ncomms12039. View