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The translin–TRAX complex (C3PO) is a ribonuclease in tRNA processing

Nature Structural & Molecular Biology volume 19, pages 824–830 (2012)Cite this article

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Abstract

Conserved translin–TRAX complexes, also known as C3POs, have been implicated in many biological processes, but how they function remains unclear. Recently, C3PO was shown to be an endoRNase that promotes RNA interference (RNAi) in animal cells. Here, we show that C3PO does not play a significant role in RNAi in the filamentous fungus Neurospora crassa. Instead, the Neurospora C3PO functions as an RNase that removes the 5′ pre-tRNA fragments after the processing of pre-tRNAs by RNase P. In addition, translin and trax mutants have elevated levels of tRNA and protein translation and are more resistant to a cell death–inducing agent. Finally, we show that C3PO is also involved in tRNA processing in mouse embryonic fibroblast cells. This study identifies the endogenous RNA substrates of C3PO and provides a potential explanation for its roles in apparently diverse biological processes.

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Figure 1: Neurospora translin and TRAX are not required for RNAi and siRNA passenger-strand removal.
Figure 2: Accumulation of sRNA species in the tsnKO and trxKO strains is dependent on the catalytic activity of the translin–TRAX complex.
Figure 3: Deep sequencing of sRNAs reveals the accumulation of 5′ pre-tRNA fragments in the tsnKO strain.
Figure 4: High levels of 5′ pre-tRNA fragments in the tsnKO and trxKO strains.
Figure 5: Dicer is required for the production of the antisense-specific sRNAs.
Figure 6: The pre-tRNA fragments are substrates of the Neurospora translin–TRAX complex.
Figure 7: Translin and TRAX regulate levels of tRNA and protein translation.

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Acknowledgements

We thank H. Yuan and Q. Ye in Y.L.'s lab at U.T. Southwestern Medical Center for technical assistance and Ying Liu and X. Ye in Q.L.'s lab for providing the recombinant Drosophila C3PO and for advice on C3PO purification. This work was supported by grants from the US National Institutes of Health (R01 GM062591 and R01 GM084283 to Y.L., R01GM084010 to Q.L. and R01GM058800 to C.C.M.) and from the Welch Foundation (I-1560 to Y.L. and I-1608 to Q.L.). C.C.M. is supported as a Howard Hughes Medical Institute Investigator.

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Authors and Affiliations

  1. Department of Physiology, The University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Liande Li & Yi Liu

  2. Howard Hughes Medical Institute, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Weifeng Gu & Craig C Mello

  3. Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA

    Weifeng Gu & Craig C Mello

  4. Department of Biochemistry, The University of Texas Southwestern Medical Center, Dallas, Texas, USA

    Chunyang Liang & Qinghua Liu

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Contributions

L.L. designed, conducted and interpreted experiments. W.G. performed sRNA sequencing and analyses. C.L. prepared RNA from MEFs. C.C.M. and Q.L. interpreted experimental results. Y.L. designed and interpreted experiments and wrote the paper.

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Correspondence to Yi Liu.

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Li, L., Gu, W., Liang, C. et al. The translin–TRAX complex (C3PO) is a ribonuclease in tRNA processing. Nat Struct Mol Biol 19, 824–830 (2012). https://doi.org/10.1038/nsmb.2337

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