Evidence map›Paper›PMID 25223788›Full record

ArticleNucleic acids research2014

Selective microRNA uridylation by Zcchc6 (TUT7) and Zcchc11 (TUT4).

James E Thornton, Peng Du, Lili Jing, Ljiljana Sjekloca, Shuibin Lin, Elena Grossi, Piotr Sliz, Leonard I Zon, Richard I Gregory

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
3.8field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

73 citing papers in PubMed, 100 citations in OpenAlex.

  1. Target-Directed miRNA Degradation: Mechanisms and Significance.Methods in molecular biology (Clifton, N.J.) · 2026
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13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

James E ThorntonStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA.
Peng DuStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA.
Lili JingStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA.
Ljiljana SjeklocaDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
Shuibin LinStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA.
Elena GrossiStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA.
Piotr SlizDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Leonard I ZonStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA Harvard Stem Cell Institute, Cambridge, MA 02138, USA Department of Genetics, Harvard Medical School, Boston, MA 02115, USA Howard Hughes Medical Institute, Boston, MA 02115, USA.
Richard I GregoryStem Cell Program, Boston Children's Hospital, Boston, MA 02115, USA Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA Harvard Stem Cell Institute, Cambridge, MA 02138, USA rgregory@enders.tch.harvard.edu.
Boston Children's Hospital · USHarvard University · US

Funding

Regulation of microRNA Biogenesis in Stem CellsR01GM086386 · NIGMS · BOSTON CHILDREN'S HOSPITAL · PI GREGORY, RICHARD I. · 2009 to 2018
$3.1M
Structural and Mechanistic Studies of Regulation of let-7 biogenesis by Lin28'R01CA163647 · NCI · HARVARD MEDICAL SCHOOL · PI SLIZ, PIOTR · 2012 to 2016
$1.7M
NCI NIH HHS R01 CA163647NCI NIH HHS R01CA163647NIGMS NIH HHS R01GM086386
6 · The paper itself

Abstract

Recent small RNA sequencing data has uncovered 3' end modification of mature microRNAs (miRNAs). This non-templated nucleotide addition can impact miRNA gene regulatory networks through the control of miRNA stability or by interfering with the repression of target mRNAs. The miRNA modifying enzymes responsible for this regulation remain largely uncharacterized. Here we describe the ability for two related terminal uridyl transferases (TUTases), Zcchc6 (TUT7) and Zcchc11 (TUT4), to 3' mono-uridylate a specific subset of miRNAs involved in cell differentiation and Homeobox (Hox) gene control. Zcchc6/11 selectively uridylates these miRNAs in vitro, and we biochemically define a bipartite sequence motif that is necessary and sufficient to confer Zcchc6/11 catalyzed uridylation. Depletion of these TUTases in cultured cells causes the selective loss of 3' mono-uridylation of many of the same miRNAs. Upon TUTase-dependent loss of uridylation, we observe a concomitant increase in non-templated 3' mono-adenylation. Furthermore, TUTase inhibition in Zebrafish embryos causes developmental defects and aberrant Hox expression. Our results uncover the molecular basis for selective miRNA mono-uridylation by Zcchc6/11, highlight the precise control of different 3' miRNA modifications in cells and have implications for miRNA and Hox gene regulation during development.

Indexed as

AnimalsDNA-Binding ProteinsGene Expression Regulation, DevelopmentalGenes, HomeoboxHumansMicroRNAsNucleotide MotifsRNA NucleotidyltransferasesUridineZebrafishDNA-Binding ProteinsMicroRNAsRNA NucleotidyltransferasesTUT4 protein, humanTUT7 protein, humanUridine

Identifiers

PMID25223788
PMCPMC4191393
OpenAlexW2139263697

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.