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Published online before print May 2, 2008
RNA, DOI: 10.1261/rna.1050408
 Copyright © 2008 RNA Society
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Competition between the Rex1 exonuclease and the La protein affects both Trf4p-mediated RNA quality control and pre-tRNA maturation

Laura A. Copela1, Cesar F. Fernandez1,3, R. Lynn Sherrer1,4, and Sandra L. Wolin1,2

1 Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06519-1418, USA
2 Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, Connecticut 06520-8114, USA

Although nascent noncoding RNAs can undergo maturation to functional RNAs or degradation by quality control pathways, the events that influence the choice of pathway are not understood. We report that the targeting of pre-tRNAs and certain other noncoding RNAs for decay by the TRAMP pathway is strongly influenced by competition between the La protein and the Rex1 exonuclease for access to their 3' ends. The La protein binds the 3' ends of many nascent noncoding RNAs, protecting them from exonucleases. We demonstrate that unspliced, end-matured, partially aminoacylated pre-tRNAs accumulate in yeast lacking the TRAMP subunit Trf4p, indicating that these pre-tRNAs normally undergo decay. By comparing RNA extracted from wild-type and mutant yeast strains, we show that Rex1p is the major exonuclease involved in pre-tRNA trailer trimming and may also function in nuclear CCA turnover. As the accumulation of end-matured pre-tRNAs in trf4{Delta} cells requires Rex1p, these pre-tRNAs are formed by exonucleolytic trimming. Accumulation of truncated forms of 5S rRNA and SRP RNA in trf4{Delta} cells also requires Rex1p. Overexpression of the La protein Lhp1p reduces both exonucleolytic pre-tRNA trimming in wild-type cells and the accumulation of defective RNAs in trf4{Delta} cells. Our experiments reveal that one consequence of Rex1p-dependent 3' trimming is the generation of aberrant RNAs that are targeted for decay by TRAMP.

Keywords: RNA quality control; tRNA maturation; exonucleases; La protein; TRAMP; Rex1p

Received February 25, 2008 ; accepted March 11, 2008.

3 Present addresses: Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, CA 90095-0001, USA;

4 Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520-8114, USA.

Reprint requests to: Sandra L. Wolin, Department of Cell Biology, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06519-1418, USA; e-mail: sandra.wolin{at}yale.edu; fax: (203) 737-1761.

Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.1050408.


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