title: tRNAs marked with CCACCA are targeted for degradation.
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.
authors.affiliation: Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. wilusz@mit.edu
authors.forename: Jeremy E
authors.initials: JE
authors.lastname: Wilusz
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Whipple
authors.forename: Eric M
authors.initials: EM
authors.lastname: Phizicky
authors.forename: Phillip A
authors.initials: PA
authors.lastname: Sharp
mesh_terms: D000818:Animals; D019843:Archaeal Proteins / Q000378:metabolism; D001483:Base Sequence; D029968:Escherichia coli Proteins / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D051379:Mice; D009690:Nucleic Acid Conformation; D026723:Polyadenylation; D026721:RNA 3' End Processing; D012316:RNA Nucleotidyltransferases / Q000378:metabolism*; D020871:RNA Stability; D012331:RNA, Fungal / Q000737:chemistry / Q000378:metabolism; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012362:RNA, Transfer, Ser / Q000737:chemistry / Q000378:metabolism; D022661:RNA, Untranslated / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016944:Sulfolobus / Q000201:enzymology
chemical_list: D019843:Archaeal Proteins; D029968:Escherichia coli Proteins; D005656:Fungal Proteins; D012331:RNA, Fungal; D012362:RNA, Transfer, Ser; D022661:RNA, Untranslated; D012343:RNA, Transfer; D012316:RNA Nucleotidyltransferases; C023198:tRNA nucleotidyltransferase
references.citation: Cell Mol Life Sci. 2010 May;67(9):1447-63
references.pmid: 20155482
references.citation: Genes Dev. 2011 Jun 1;25(11):1173-84
references.pmid: 21632824
references.citation: Genome Res. 2009 Mar;19(3):347-59
references.pmid: 19106332
references.citation: Cell. 2006 Sep 22;126(6):1065-77
references.pmid: 16962654
references.citation: Cell. 2009 Jul 23;138(2):215-9
references.pmid: 19632169
references.citation: RNA. 2004 Apr;10(4):615-21
references.pmid: 15037771
references.citation: RNA. 2010 Feb;16(2):259-66
references.pmid: 20007330
references.citation: Cell. 2008 Nov 28;135(5):919-32
references.pmid: 19041754
references.citation: Nature. 2004 Aug 5;430(7000):700-4
references.pmid: 15295603
references.citation: Mol Cell. 2008 Mar 28;29(6):717-28
references.pmid: 18374646
references.citation: Curr Opin Struct Biol. 2006 Feb;16(1):12-7
references.pmid: 16364630
references.citation: Genes Dev. 2008 May 15;22(10):1369-80
references.pmid: 18443146
references.citation: RNA. 1996 Sep;2(9):895-908
references.pmid: 8809016
references.citation: RNA. 1998 Mar;4(3):276-84
references.pmid: 9510330
references.citation: Mol Cell. 2006 Jan 6;21(1):87-96
references.pmid: 16387656
references.citation: Genes Dev. 2010 Sep 1;24(17):1832-60
references.pmid: 20810645
references.citation: J Mol Biol. 2003 May 16;328(5):985-94
references.pmid: 12729736
references.citation: J Biol Chem. 2001 Oct 26;276(43):40041-9
references.pmid: 11504732
references.citation: Prog Nucleic Acid Res Mol Biol. 1979;22:1-69
references.pmid: 392600
references.citation: J Biol Chem. 1998 Nov 6;273(45):29693-700
references.pmid: 9792681
references.citation: RNA. 2008 Jan;14(1):158-69
references.pmid: 18025252
references.citation: EMBO J. 1998 Jun 1;17(11):3197-206
references.pmid: 9606201
references.citation: Science. 2000 Aug 11;289(5481):905-20
references.pmid: 10937989
references.citation: Science. 2010 Nov 12;330(6006):937-40
references.pmid: 21071662
references.citation: Nature. 2004 Aug 5;430(7000):640-5
references.pmid: 15295590
references.citation: Science. 1993 Feb 5;259(5096):812-6
references.pmid: 8430334
references.citation: J Biol Chem. 2006 Oct 6;281(40):29769-75
references.pmid: 16893880