TRNA Metabolism and Neurodevelopmental Disorders

Overview

Journal Annu Rev Genomics Hum Genet

Publisher Annual Reviews

Specialty Genetics

Date 2019 May 15

PMID 31082281

Citations 42

Authors

Ashleigh E Schaffer

Otis Pinkard

Jeffery M Coller

Affiliations

Soon will be listed here.

Abstract

tRNAs are short noncoding RNAs required for protein translation. The human genome includes more than 600 putative tRNA genes, many of which are considered redundant. tRNA transcripts are subject to tightly controlled, multistep maturation processes that lead to the removal of flanking sequences and the addition of nontemplated nucleotides. Furthermore, tRNAs are highly structured and posttranscriptionally modified. Together, these unique features have impeded the adoption of modern genomics and transcriptomics technologies for tRNA studies. Nevertheless, it has become apparent from human neurogenetic research that many tRNA biogenesis proteins cause brain abnormalities and other neurological disorders when mutated. The cerebral cortex, cerebellum, and peripheral nervous system show defects, impairment, and degeneration upon tRNA misregulation, suggesting that they are particularly sensitive to changes in tRNA expression or function. An integrated approach to identify tRNA species and contextually characterize tRNA function will be imperative to drive future tool development and novel therapeutic design for tRNA-associated disorders.

Citing Articles

Transfer RNA Levels Are Tuned to Support Differentiation During Drosophila Neurogenesis.

Wint R, Cleary M Genes (Basel). 2025; 15(12.

PMID: 39766869 PMC: 11675937. DOI: 10.3390/genes15121602.

tRNA modification enzyme-dependent redox homeostasis regulates synapse formation and memory.

Madhwani K, Sayied S, Ogata C, Hogan C, Lentini J, Mallik M Proc Natl Acad Sci U S A. 2024; 121(46):e2317864121.

PMID: 39495910 PMC: 11572970. DOI: 10.1073/pnas.2317864121.

Transfer RNA levels are tuned to support differentiation during Drosophila neurogenesis.

Wint R, Cleary M bioRxiv. 2024; .

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RTP801 interacts with the tRNA ligase complex and dysregulates its RNA ligase activity in Alzheimer's disease.

Campoy-Campos G, Solana-Balaguer J, Guisado-Corcoll A, Chicote-Gonzalez A, Garcia-Segura P, Perez-Sisques L Nucleic Acids Res. 2024; 52(18):11158-11176.

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Human organoid model of pontocerebellar hypoplasia 2a recapitulates brain region-specific size differences.

Kagermeier T, Hauser S, Sarieva K, Laugwitz L, Groeschel S, Janzarik W Dis Model Mech. 2024; 17(7).

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References

Lipowsky G, Bischoff F, Izaurralde E, Kutay U, Schafer S, Gross H . Coordination of tRNA nuclear export with processing of tRNA. RNA. 1999; 5(4):539-49. PMC: 1369780. DOI: 10.1017/s1355838299982134. View

Mikkelsen N, Brannvall M, Virtanen A, Kirsebom L . Inhibition of RNase P RNA cleavage by aminoglycosides. Proc Natl Acad Sci U S A. 1999; 96(11):6155-60. PMC: 26851. DOI: 10.1073/pnas.96.11.6155. View

Flores A, Briand J, Gadal O, Andrau J, Rubbi L, Van Mullem V . A protein-protein interaction map of yeast RNA polymerase III. Proc Natl Acad Sci U S A. 1999; 96(14):7815-20. PMC: 22144. DOI: 10.1073/pnas.96.14.7815. View

Bovee M, Yan W, Sproat B, Francklyn C . tRNA discrimination at the binding step by a class II aminoacyl-tRNA synthetase. Biochemistry. 1999; 38(41):13725-35. DOI: 10.1021/bi991182g. View

Foster P, Huang L, Santi D, Stroud R . The structural basis for tRNA recognition and pseudouridine formation by pseudouridine synthase I. Nat Struct Biol. 2000; 7(1):23-7. DOI: 10.1038/71219. View

Intine R, Sakulich A, Koduru S, Huang Y, Pierstorff E, Goodier J . Control of transfer RNA maturation by phosphorylation of the human La antigen on serine 366. Mol Cell. 2000; 6(2):339-48. DOI: 10.1016/s1097-2765(00)00034-4. View

Zschocke J, Ruiter J, Brand J, Lindner M, Hoffmann G, Wanders R . Progressive infantile neurodegeneration caused by 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency: a novel inborn error of branched-chain fatty acid and isoleucine metabolism. Pediatr Res. 2000; 48(6):852-5. DOI: 10.1203/00006450-200012000-00025. View

Paul R, Lazarev D, Altman S . Characterization of RNase P from Thermotoga maritima. Nucleic Acids Res. 2001; 29(4):880-5. PMC: 29617. DOI: 10.1093/nar/29.4.880. View

Rodnina M, Wintermeyer W . Ribosome fidelity: tRNA discrimination, proofreading and induced fit. Trends Biochem Sci. 2001; 26(2):124-30. DOI: 10.1016/s0968-0004(00)01737-0. View

10.

Bataillard M, Chatzoglou E, Rumbach L, Sternberg D, Tournade A, Laforet P . Atypical MELAS syndrome associated with a new mitochondrial tRNA glutamine point mutation. Neurology. 2001; 56(3):405-7. DOI: 10.1212/wnl.56.3.405. View

11.

Taylor R, Taylor G, Durham S, Turnbull D . The determination of complete human mitochondrial DNA sequences in single cells: implications for the study of somatic mitochondrial DNA point mutations. Nucleic Acids Res. 2001; 29(15):E74-4. PMC: 55839. DOI: 10.1093/nar/29.15.e74. View

12.

Nagaike T, Suzuki T, Tomari Y, Negayama F, Watanabe K, Ueda T . Identification and characterization of mammalian mitochondrial tRNA nucleotidyltransferases. J Biol Chem. 2001; 276(43):40041-9. DOI: 10.1074/jbc.M106202200. View

13.

Urbonavicius J, Qian Q, Durand J, Hagervall T, Bjork G . Improvement of reading frame maintenance is a common function for several tRNA modifications. EMBO J. 2001; 20(17):4863-73. PMC: 125605. DOI: 10.1093/emboj/20.17.4863. View

14.

Maillet L, Collart M . Interaction between Not1p, a component of the Ccr4-not complex, a global regulator of transcription, and Dhh1p, a putative RNA helicase. J Biol Chem. 2001; 277(4):2835-42. DOI: 10.1074/jbc.M107979200. View

15.

Rossmanith W, Potuschak T . Difference between mitochondrial RNase P and nuclear RNase P. Mol Cell Biol. 2001; 21(23):8236-7. PMC: 99988. DOI: 10.1128/MCB.21.23.8236-8237.2001. View

16.

Beier H, Grimm M . Misreading of termination codons in eukaryotes by natural nonsense suppressor tRNAs. Nucleic Acids Res. 2001; 29(23):4767-82. PMC: 96686. DOI: 10.1093/nar/29.23.4767. View

17.

Hoang C, Ferre-DAmare A . Cocrystal structure of a tRNA Psi55 pseudouridine synthase: nucleotide flipping by an RNA-modifying enzyme. Cell. 2002; 107(7):929-39. DOI: 10.1016/s0092-8674(01)00618-3. View

18.

Coller J, Tucker M, Sheth U, Parker R . The DEAD box helicase, Dhh1p, functions in mRNA decapping and interacts with both the decapping and deadenylase complexes. RNA. 2002; 7(12):1717-27. PMC: 1370212. DOI: 10.1017/s135583820101994x. View

19.

Jarrous N . Human ribonuclease P: subunits, function, and intranuclear localization. RNA. 2002; 8(1):1-7. PMC: 1370226. DOI: 10.1017/s1355838202011184. View

20.

Schiffer S, Rosch S, Marchfelder A . Assigning a function to a conserved group of proteins: the tRNA 3'-processing enzymes. EMBO J. 2002; 21(11):2769-77. PMC: 126033. DOI: 10.1093/emboj/21.11.2769. View