The process of tRNA splicing entails removal of an intron by TSEN (tRNA–splicing endonuclease) and ligation of the resulting exon halves to generate functional tRNAs. In mammalian cells, the RNA kinase CLP1 (cleavage and polyadenylation factor I subunit) associates with TSEN and phosphorylates the 3′ exon at the 5′ end in vitro, suggesting a role for CLP1 in tRNA splicing. Interestingly, recent data suggest that the ATP-binding and/or hydrolysis capacity of CLP1 is required to enhance pre-tRNA cleavage. In vivo, the lack of CLP1 kinase activity leads to progressive motor neuron loss and accumulation of novel 5′ leader–5′ exon tRNA fragments. We have extended the investigation of the biochemical requirements in pre-tRNA splicing and found that β–γ-hydrolysable ATP is crucial for the productive generation of exon halves. In addition, we provide evidence that phosphorylation of the TSEN complex components supports efficient pre-tRNA cleavage. Taken together, our data improve the mechanistic understanding of mammalian pre-tRNA processing and its regulation.
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August 2013
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Conference Article|
July 18 2013
Intron excision from precursor tRNA molecules in mammalian cells requires ATP hydrolysis and phosphorylation of tRNA-splicing endonuclease components
Barbara Mair;
Barbara Mair
1
*IMBA–Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria
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Johannes Popow;
Johannes Popow
*IMBA–Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria
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Karl Mechtler;
Karl Mechtler
†IMP–Research Institute of Molecular Pathology, Protein Chemistry Department, A-1030 Vienna, Austria
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Stefan Weitzer;
Stefan Weitzer
2
*IMBA–Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria
2Correspondence may be addressed to either of these authors (emailstefan.weitzer@imba.oeaw.ac.at or javier.martinez@imba.oeaw.ac.at).
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Javier Martinez
Javier Martinez
2
*IMBA–Institute of Molecular Biotechnology of the Austrian Academy of Sciences, A-1030 Vienna, Austria
2Correspondence may be addressed to either of these authors (emailstefan.weitzer@imba.oeaw.ac.at or javier.martinez@imba.oeaw.ac.at).
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Publisher: Portland Press Ltd
Received:
March 05 2013
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem Soc Trans (2013) 41 (4): 831–837.
Article history
Received:
March 05 2013
Citation
Barbara Mair, Johannes Popow, Karl Mechtler, Stefan Weitzer, Javier Martinez; Intron excision from precursor tRNA molecules in mammalian cells requires ATP hydrolysis and phosphorylation of tRNA-splicing endonuclease components. Biochem Soc Trans 1 August 2013; 41 (4): 831–837. doi: https://doi.org/10.1042/BST20130025
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