The Cid1 family of non‐canonical poly(A) polymerases

Stevenson, Abigail L.; Norbury, Chris J.

doi:10.1002/yea.1408

Cited by 57 publications

(62 citation statements)

References 57 publications

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“…Modeling of additional RNA residues into the ternary complex provides a rationale for the pronounced selectivity of trypanosomal TUTases toward the specific base at the 3Ј end of the RNA substrate. Thus, our studies establish a structural model for UTP/ATP recognition by a conserved catalytic module shared among RNA uridylyltransferases and noncanonical PAPs, a group of enzymes involved in a wide variety of RNA processing events in eukaryotes (1,16).…”

mentioning

confidence: 69%

Dual role of the RNA substrate in selectivity and catalysis by terminal uridylyl transferases

Stagno

Aphasizheva²,

Aphasizhev³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Terminal RNA uridylyltransferases (TUTases) catalyze templateindependent UMP addition to the 3 hydroxyl of RNA. TUTases belong to the DNA polymerase ␤ superfamily of nucleotidyltransferases that share a conserved catalytic domain bearing three metal-binding carboxylate residues. We have previously determined crystal structures of the UTP-bound and apo forms of the minimal trypanosomal TUTase, TbTUT4, which is composed solely of the N-terminal catalytic and C-terminal base-recognition domains. Here we report crystal structures of TbTUT4 with bound CTP, GTP, and ATP, demonstrating nearly perfect superposition of the triphosphate moieties with that of the UTP substrate. Consequently, at physiological nucleoside 5-triphosphate concentrations, the protein-uracil base interactions alone are not sufficient to confer UTP selectivity. To resolve this ambiguity, we determined the crystal structure of a prereaction ternary complex composed of UTP, TbTUT4, and UMP, which mimics an RNA substrate, and the postreaction complex of TbTUT4 with UpU dinucleotide. The UMP pyrimidine ring stacks against the uracil base of the bound UTP, which on its other face also stacks with an essential tyrosine. In contrast, the different orientation of the purine bases observed in cocrystals with ATP and GTP prevents this triple stacking, precluding productive binding of the RNA. The 3 hydroxyl of the bound UMP is poised for in-line nucleophilic attack while contributing to the formation of a binding site for a second catalytic metal ion. We propose a dual role for RNA substrates in TUTase-catalyzed reactions: contribution to selective incorporation of the cognate nucleoside and shaping of the catalytic metal binding site.crystal structure ͉ nucleotidyl transferase ͉ RNA editing ͉ Trypanosoma ͉ terminal RNA uridylyltransferase poly(A) polymerase T erminal RNA uridylyltransferases (TUTases) are phylogenetically widespread and functionally divergent enzymes that catalyze template-independent transfer of UMP residues to the 3Ј hydroxyl group of RNA (1). TUTases belong to the polymerase ␤ nucleotidyltransferase superfamily, which is characterized by the presence of the signature motif hG[G/S]X9-13Dh[D/E]h (X, any; h, hydrophobic amino acids) (2) and also includes poly(A) polymerases (PAPs), ATP(CTP):tRNA nucleotidyltransferases, terminal deoxy nucleotidyltransferases, protein nucleotidyltransferases, 2Ј-5Ј oligo(A) synthetases, and antibiotic resistance nucleotidyltransferases (3). TUTase activities have been reported in mammalian cells, plants, and parasitic protists from the order Kinetoplastida, Trypanosoma brucei, and Leishmania ssp. (1). Extensive uridine insertion/deletion editing in mitochondria of trypanosomatids requires 3Ј uridylylation of guide RNAs by RNA editing TUTase 1 (RET1) (4) and insertion of Us into messenger RNAs by RNA editing TUTase 2 (RET2) (5, 6). In addition to mitochondrial RNA editing TUTases, TUT3 (7) and TUT4 (8), cytoplasmic uridylyl transferases have been reported in T. brucei. Human cells apparently possess several ...

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mentioning

confidence: 69%

Dual role of the RNA substrate in selectivity and catalysis by terminal uridylyl transferases

Stagno

Aphasizheva²,

Aphasizhev³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…C. elegans pup-1 also interacts genetically with chk-1, a known S/M checkpoint control gene. In S. pombe, cid1 mutants are sensitized to a combination of HU and caffeine that overrides the S/M checkpoint (Wang et al 2000); similarly, SpCID1 overexpression partially suppresses the HU sensitivity of mutations in a protein kinase that is required for S/M and DNA damage checkpoint control (RAD3, RAD9, and RAD17) (for review, see Stevenson and Norbury 2006). The S. pombe cytoplasmic PAP, CID13, is also involved in checkpoint control (Read et al 2002), hinting that the PAP and PUP pathways may interact.…”

Section: Discussionmentioning

confidence: 99%

A family of poly(U) polymerases

Kwak¹,

Wickens²

2007

RNA

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146

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The GLD-2 family of poly(A) polymerases add successive AMP monomers to the 39 end of specific RNAs, forming a poly(A) tail. Here, we identify a new group of GLD-2-related nucleotidyl transferases from Arabidopsis, Schizosaccharomyces pombe, Caenorhabditis elegans, and humans. Like GLD-2, these enzymes are template independent and add nucleotides to the 39 end of an RNA substrate. However, these new enzymes, which we refer to as poly(U) polymerases, add poly(U) rather than poly(A) to their RNA substrates.

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“…rNTrs are currently classified into canonical and noncanonical rNtrs [8,12], according to their functional and structural attributes. The canonical rNTrs include the classical PAPs first described in eukaryotes, which polyadenylate pre-mRNAs in the nucleus and in some cases, in the cytoplasm [13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Determinants of substrate specificity in RNA-dependent nucleotidyl transferases

Martín

Doublié

Keller

2008

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Poly(A) polymerases were identified almost fifty years ago as enzymes that add multiple AMP residues to the 3′ ends of primer RNAs without use of a template from ATP as cosubstrate and with release of pyrophosphate. Based on sequence homology of a signature motif in the catalytic domain, poly(A) polymerases were later found to belong to a superfamily of nucleotidyl transferases acting on a very diverse array of substrates. Enzymes belonging to the superfamily can add from single nucleotides of AMP, CMP or UMP to RNA, antibiotics and proteins but also homopolymers of many hundred residues to the 3′ ends of RNA molecules.The recently reported structures of several nucleotidyl transferases facilitate the study of the catalytic mechanisms of these very diverse enzymes. Numerous structures of CCA-adding enzymes have now revealed all steps in the formation of a CCA tail at the 3′ end of tRNAs. In addition, structures of poly(A) polymerases and uridylyl transferases are now available as binary and ternary complexes with incoming nucleotide and RNA primer. Some of these proteins undergo significant conformational changes after substrate binding. This is proposed to be an indication for an induced fit mechanism that drives substrate selection and leads to catalysis. Insights from recent structures of ternary complexes indicate an important role for the primer molecule in selecting the incoming nucleotide.

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The Cid1 family of non‐canonical poly(A) polymerases

Cited by 57 publications

References 57 publications

Dual role of the RNA substrate in selectivity and catalysis by terminal uridylyl transferases

Dual role of the RNA substrate in selectivity and catalysis by terminal uridylyl transferases

A family of poly(U) polymerases

Determinants of substrate specificity in RNA-dependent nucleotidyl transferases

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