tRNAs marked with CCACCA are targeted for degradation.

Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Science (Impact Factor: 31.48). 11/2011; 334(6057):817-21. DOI: 10.1126/science.1213671
Source: PubMed

ABSTRACT The CCA-adding enzyme [ATP(CTP):tRNA nucleotidyltransferase] adds CCA to the 3' ends of transfer RNAs (tRNAs), a critical step in tRNA biogenesis that generates the amino acid attachment site. We found that the CCA-adding enzyme plays a key role in tRNA quality control by selectively marking structurally unstable tRNAs and tRNA-like small RNAs for degradation. Instead of adding CCA to the 3' ends of these transcripts, CCA-adding enzymes from all three kingdoms of life add CCACCA. In addition, hypomodified mature tRNAs are subjected to CCACCA addition as part of a rapid tRNA decay pathway in vivo. We conjecture that CCACCA addition is a universal mechanism for controlling tRNA levels and preventing errors in translation.

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Available from: Joseph Whipple, Mar 26, 2014
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    • "The CCA-3 is also required for tRNA quality control. The tandem C 74 C 75 A 76 C 77 C 78 A 79 -3 sequence, added onto the 3 -end of tRNA, acts as a degradation signal for dysfunctional tRNA molecules (Wilusz et al., 2011). The CCA-3 is synthesized and/or repaired by the CCA-adding enzyme, CTP:(ATP) tRNA nucleotidyltransferase (NT), using CTP and ATP as substrates (Deutscher, 1990; Weiner, 2004). "
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    ABSTRACT: The universal 3'-terminal CCA sequence of tRNA is built and/or synthesized by the CCA-adding enzyme, CTP:(ATP) tRNA nucleotidyltransferase. This RNA polymerase has no nucleic acid template, but faithfully synthesizes the defined CCA sequence on the 3'-terminus of tRNA at one time, using CTP and ATP as substrates. The mystery of CCA-addition without a nucleic acid template by unique RNA polymerases has long fascinated researchers in the field of RNA enzymology. In this review, the mechanisms of RNA polymerization by the remarkable CCA-adding enzyme and its related enzymes are presented, based on their structural features.
    Frontiers in Genetics 02/2014; 5:36. DOI:10.3389/fgene.2014.00036
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    • "The invariant CCA-3 0 is required for amino acid attachment onto the 3 0 end of the tRNA by aminoacyl-tRNA synthases (Sprinzl and Cramer, 1979), and for peptide-bond formation on ribosomes (Green and Noller, 1997; Kim and Green, 1999; Nissen et al., 2000). The CCA-3 0 is also required for tRNA quality control (Wilusz et al., 2011). "
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    ABSTRACT: The 3'-terminal CCA (CCA-3' at positions 74-76) of tRNA is synthesized by CCA-adding enzyme using CTP and ATP as substrates, without a nucleic acid template. In Aquifex aeolicus, CC-adding and A-adding enzymes collaboratively synthesize the CCA-3'. The mechanism of CCA-3' synthesis by these two enzymes remained obscure. We now present crystal structures representing CC addition onto tRNA by A. aeolicus CC-adding enzyme. After C74 addition in an enclosed active pocket and pyrophosphate release, the tRNA translocates and rotates relative to the enzyme, and C75 addition occurs in the same active pocket as C74 addition. At both the C74-adding and C75-adding stages, CTP is selected by Watson-Crick-like hydrogen bonds between the cytosine of CTP and conserved Asp and Arg residues in the pocket. After C74C75 addition and pyrophosphate release, the tRNA translocates further and drops off the enzyme, and the CC-adding enzyme terminates RNA polymerization.
    Structure 12/2013; 22(2). DOI:10.1016/j.str.2013.12.002 · 6.79 Impact Factor
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    • "Now that instances of degradation of the most ubiquitous stable RNAs, including tRNAs, are revealed in increasing numbers (Thompson and Parker , 2009 ; Wilusz et al. , 2011 ; Dewe et al. , 2012 ), a rather obvious question arises: how stable are the other stable ribonucleoproteins ? These include the RNase P ribonucleoprotein, the various spliceosomes , and small nucleolar ribonucleoproteins involved in RNA modification, and others, all of which could benefit from quality control and regulation at the level of degradation . "
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    ABSTRACT: Abstract This review takes a comparative look at the various scenarios where ribosomes are degraded in bacteria and eukaryotes with emphasis on studies involving Escherichia coli and Saccharomyces cerevisiae. While the molecular mechanisms of degradation in bacteria and yeast appear somewhat different we argue that the underlying causes of ribosome degradation are remarkably similar. In both model organisms during ribosomal assembly partially formed pre-ribosomal particles can be degraded by at least two different sequentially acting quality control pathways and fully assembled but functionally faulty ribosomes can be degraded in a separate quality control pathway. In addition, ribosomes that are both structurally and functionally sound can be degraded as an adaptive measure to stress.
    Biological Chemistry 03/2013; 394(7). DOI:10.1515/hsz-2013-0133 · 2.69 Impact Factor
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