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C to U editing at position 32 of the anticodon loop precedes tRNA 5' leader removal in trypanosomatids.

Gaston KW, Rubio MA, Spears JL, Pastar I, Papavasiliou FN, Alfonzo JD - Nucleic Acids Res. (2007)

Bottom Line: These involve 5' and 3' end trimming as well as the addition of a significant number of chemical modifications, including RNA editing.We also show that C to U editing is a nuclear event while A to I is cytoplasmic, where C to U editing at position 32 occurs in the precursor tRNA prior to 5' leader removal.Our data supports the view that C to U editing is more widespread than previously thought and is part of a stepwise process in the maturation of tRNAs in these organisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, The Ohio State RNA Group, The Ohio State University, Columbus, Ohio 43210, USA.

ABSTRACT
In all organisms, precursor tRNAs are processed into mature functional units by post-transcriptional changes. These involve 5' and 3' end trimming as well as the addition of a significant number of chemical modifications, including RNA editing. The only known example of non-organellar C to U editing of tRNAs occurs in trypanosomatids. In this system, editing at position 32 of the anticodon loop of tRNA(Thr)(AGU) stimulates, but is not required for, the subsequent formation of inosine at position 34. In the present work, we expand the number of C to U edited tRNAs to include all the threonyl tRNA isoacceptors. Notably, the absence of a naturally encoded adenosine, at position 34, in two of these isoacceptors demonstrates that A to I is not required for C to U editing. We also show that C to U editing is a nuclear event while A to I is cytoplasmic, where C to U editing at position 32 occurs in the precursor tRNA prior to 5' leader removal. Our data supports the view that C to U editing is more widespread than previously thought and is part of a stepwise process in the maturation of tRNAs in these organisms.

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A schematic model of how in vivo distribution of both editing events and the localization of the editing enzyme may play a role in regulating editing levels.
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Figure 7: A schematic model of how in vivo distribution of both editing events and the localization of the editing enzyme may play a role in regulating editing levels.

Mentions: In light of our previous reports suggesting that TbADAT2p plays a role in both events, predictably this enzyme should also localize to both the nucleus and cytoplasm. In line with this proposal, we have shown that although the bulk of TbADAT2p signal is found in the cytoplasm, a measurable amount is also observed to shuttle to the nucleus. We propose a model (Figure 7) by which sub-cellular localization of the eukaryotic editing deaminases may alter their specificity. In the trypanosomatid example, this model suggests that TbADAT2p may have different specificity depending on two variables: its sub-cellular localization (i.e. nuclear, cytoplasmic and maybe even mitochondrial) or its association with different protein subunits. The first part of the model is supported by the nuclear localization experiments. The second part of the model is more difficult to test, as it requires prior knowledge of who associates with whom within a cell. However, in a way nature has already performed the experiment for us. ADAT2p and ADAT3p, cyitidine deaminases in terms of primary sequence, pair up in the form of a heterodimer and indeed act as adenosine deaminases in tRNA (19,21). Finally, beyond what sub-unit distribution and altered specificity may contribute to editing regulation, the role that either C to U editing and/or its nuclear localization plays in these cells is not yet clear. However, taken together, the data presented here show that these types of editing events may affect many more tRNA substrates than previously imagined and that sub-cellular localization as well as the order of tRNA processing may play crucial roles in the regulation of tRNA function in these cells.Figure 7.


C to U editing at position 32 of the anticodon loop precedes tRNA 5' leader removal in trypanosomatids.

Gaston KW, Rubio MA, Spears JL, Pastar I, Papavasiliou FN, Alfonzo JD - Nucleic Acids Res. (2007)

A schematic model of how in vivo distribution of both editing events and the localization of the editing enzyme may play a role in regulating editing levels.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2175311&req=5

Figure 7: A schematic model of how in vivo distribution of both editing events and the localization of the editing enzyme may play a role in regulating editing levels.
Mentions: In light of our previous reports suggesting that TbADAT2p plays a role in both events, predictably this enzyme should also localize to both the nucleus and cytoplasm. In line with this proposal, we have shown that although the bulk of TbADAT2p signal is found in the cytoplasm, a measurable amount is also observed to shuttle to the nucleus. We propose a model (Figure 7) by which sub-cellular localization of the eukaryotic editing deaminases may alter their specificity. In the trypanosomatid example, this model suggests that TbADAT2p may have different specificity depending on two variables: its sub-cellular localization (i.e. nuclear, cytoplasmic and maybe even mitochondrial) or its association with different protein subunits. The first part of the model is supported by the nuclear localization experiments. The second part of the model is more difficult to test, as it requires prior knowledge of who associates with whom within a cell. However, in a way nature has already performed the experiment for us. ADAT2p and ADAT3p, cyitidine deaminases in terms of primary sequence, pair up in the form of a heterodimer and indeed act as adenosine deaminases in tRNA (19,21). Finally, beyond what sub-unit distribution and altered specificity may contribute to editing regulation, the role that either C to U editing and/or its nuclear localization plays in these cells is not yet clear. However, taken together, the data presented here show that these types of editing events may affect many more tRNA substrates than previously imagined and that sub-cellular localization as well as the order of tRNA processing may play crucial roles in the regulation of tRNA function in these cells.Figure 7.

Bottom Line: These involve 5' and 3' end trimming as well as the addition of a significant number of chemical modifications, including RNA editing.We also show that C to U editing is a nuclear event while A to I is cytoplasmic, where C to U editing at position 32 occurs in the precursor tRNA prior to 5' leader removal.Our data supports the view that C to U editing is more widespread than previously thought and is part of a stepwise process in the maturation of tRNAs in these organisms.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, The Ohio State RNA Group, The Ohio State University, Columbus, Ohio 43210, USA.

ABSTRACT
In all organisms, precursor tRNAs are processed into mature functional units by post-transcriptional changes. These involve 5' and 3' end trimming as well as the addition of a significant number of chemical modifications, including RNA editing. The only known example of non-organellar C to U editing of tRNAs occurs in trypanosomatids. In this system, editing at position 32 of the anticodon loop of tRNA(Thr)(AGU) stimulates, but is not required for, the subsequent formation of inosine at position 34. In the present work, we expand the number of C to U edited tRNAs to include all the threonyl tRNA isoacceptors. Notably, the absence of a naturally encoded adenosine, at position 34, in two of these isoacceptors demonstrates that A to I is not required for C to U editing. We also show that C to U editing is a nuclear event while A to I is cytoplasmic, where C to U editing at position 32 occurs in the precursor tRNA prior to 5' leader removal. Our data supports the view that C to U editing is more widespread than previously thought and is part of a stepwise process in the maturation of tRNAs in these organisms.

Show MeSH
Related in: MedlinePlus