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: 33.61). 11/2011; 334(6057):817-21. DOI: 10.1126/science.1213671
Source: PubMed


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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    • "MEN ε is characterized by poly A at its 3 1 end, whereas, similar to the lncRNA (MALAT1), the 3 1 end of MEN β consists of a triple helix structure[129]. Intriguingly, the structure of MEN β is more stable in various species, and the reason for this is currently under investigation[130]. It is currently accepted that the explanation for the various functions of lncRNAs lies in their multiple structures. "

    Full-text · Article · Jan 2016 · International Journal of Molecular Sciences
    • "However, unlike mascRNA, the MEN β tRNA-like small RNA is structurally unstable (due to presence of a mismatch or multiple G–U wobbles in its acceptor stem) (Fig. 2B), causing it to be marked with CCACCA and rapidly degraded in most mouse and human cells [109] [110]. Interestingly, the MEN β tRNA-like small RNA is structurally stable in many other species, including monkeys, allowing it to be marked with CCA and accumulate in cells [109]. As its function is unknown, it is still unclear why the MEN β tRNA-like small RNA is stable in only some species. "
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    ABSTRACT: Most of the human genome is transcribed, yielding a complex network of transcripts that includes tens of thousands of long noncoding RNAs. Many of these transcripts have a 5' cap and a poly(A) tail, yet some of the most abundant long noncoding RNAs are processed in unexpected ways and lack these canonical structures. Here, I highlight the mechanisms by which several of these well-characterized noncoding RNAs are generated, stabilized, and function. The MALAT1 and MEN β (NEAT1_2) long noncoding RNAs each accumulate to high levels in the nucleus, where they play critical roles in cancer progression and the formation of nuclear paraspeckles, respectively. Nevertheless, MALAT1 and MEN β are not polyadenylated as the tRNA biogenesis machinery generates their mature 3' ends. In place of a poly(A) tail, these transcripts are stabilized by highly conserved triple helical structures. Sno-lncRNAs likewise lack poly(A) tails and instead have snoRNA structures at their 5' and 3' ends. Recent work has additionally identified a number of abundant circular RNAs generated by the pre-mRNA splicing machinery that are resistant to degradation by exonucleases. As these various transcripts use non-canonical strategies to ensure their stability, it is becoming increasingly clear that long noncoding RNAs may often be regulated by unique post-transcriptional control mechanisms. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Jun 2015 · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
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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.
    Full-text · Article · Feb 2014 · Frontiers in Genetics
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