ArticleRNA (New York, N.Y.)2016
Nucleotide specificity of the human terminal nucleotidyltransferase Gld2 (TUT2).
Article in RNA (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- TENT5-mediated polyadenylation of mRNAs encoding secreted proteins is essential for gametogenesis in mice.Nature communications · 2024Article
- Article
- TENT2, TUT4, and TUT7 selectively regulate miRNA sequence and abundance.Nature communications · 2022Article
- Article
- Gld2 activity and RNA specificity is dynamically regulated by phosphorylation and interaction with QKI-7.RNA biology · 2021Article
- Structural and functional characterization of multiple myeloma associated cytoplasmic poly(A) polymerase FAM46C.Cancer communications (London, England) · 2021Article
- Oocyte meiosis-coupled poly(A) polymerase α phosphorylation and activation trigger maternal mRNA translation in mice.Nucleic acids research · 2021Article
- Regulation of RNA stability at the 3' end.Biological chemistry · 2021Review
- Structures of mammalian GLD-2 proteins reveal molecular basis of their functional diversity in mRNA and microRNA processing.Nucleic acids research · 2020Article
- A tale of non-canonical tails: gene regulation by post-transcriptional RNA tailing.Nature reviews. Molecular cell biology · 2020Review
- Gld2 activity is regulated by phosphorylation in the N-terminal domain.RNA biology · 2019Article
- Unbiased screen of RNA tailing activities reveals a poly(UG) polymerase.Nature methods · 2019Article
- RNA surveillance by uridylation-dependent RNA decay in Schizosaccharomyces pombe.Nucleic acids research · 2019Article
- Identifying and characterizing functional 3' nucleotide addition in the miRNA pathway.Methods (San Diego, Calif.) · 2019Review
- The role of 3' end uridylation in RNA metabolism and cellular physiology.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
- Terminal nucleotidyl transferases (TENTs) in mammalian RNA metabolism.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
- 3' RNA Uridylation in Epitranscriptomics, Gene Regulation, and Disease.Frontiers in molecular biosciences · 2018Review
- Biochemical and structural bioinformatics studies of fungal CutA nucleotidyltransferases explain their unusual specificity toward CTP and increased tendency for cytidine incorporation at the 3'-terminal positions of synthesized tails.RNA (New York, N.Y.) · 2017Article
- Polyadenylation is the key aspect of GLD-2 function inRNA (New York, N.Y.) · 2017Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The nontemplated addition of single or multiple nucleotides to RNA transcripts is an efficient means to control RNA stability and processing. Cytoplasmic RNA adenylation and the less well-known uridylation are post-transcriptional mechanisms regulating RNA maturation, activity, and degradation. Gld2 is a member of the noncanonical poly(A) polymerases, which include enzymes with varying nucleotide specificity, ranging from strictly ATP to ambiguous to exclusive UTP adding enzymes. Human Gld2 has been associated with transcript stabilizing miRNA monoadenylation and cytoplasmic mRNA polyadenylation. Most recent data have uncovered an unexpected miRNA uridylation activity, which promotes miRNA maturation. These conflicting data raise the question of Gld2 nucleotide specificity. Here, we biochemically characterized human Gld2 and demonstrated that it is a bona fide adenylyltransferase with only weak activity toward other nucleotides. Despite its sequence similarity with uridylyltransferases (TUT4, TUT7), Gld2 displays an 83-fold preference of ATP over UTP. Gld2 is a promiscuous enzyme, with activity toward miRNA, pre-miRNA, and polyadenylated RNA substrates. Apo-Gld2 activity is restricted to adding single nucleotides and processivity likely relies on additional RNA-binding proteins. A phylogeny of the PAP/TUTase superfamily suggests that uridylyltransferases, which are derived from distinct adenylyltransferase ancestors, arose multiple times during evolution via insertion of an active site histidine. A corresponding histidine insertion into the Gld2 active site alters substrate specificity from ATP to UTP.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.