Browse
Submit Data
Databases
API
Help

Dataset Information

5 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Multi-domain utilization by TUT4 and TUT7 in control of let-7 biogenesis.

ABSTRACT: The uridyl transferases TUT4 and TUT7 (collectively called TUT4(7)) switch between two modes of activity, either promoting expression of let-7 microRNA (monoU) or marking it for degradation (oligoU). Lin28 modulates the switch via recruitment of TUT4(7) to the precursor pre-let-7 in stem cells and human cancers. We found that TUT4(7) utilize two multidomain functional modules during the switch from monoU to oligoU. The catalytic module (CM) is essential for both activities, while the Lin28-interacting module (LIM) is indispensable for oligoU. A TUT7 CM structure trapped in the monoU activity staterevealed a duplex-RNA-binding pocket that orients group II pre-let-7 hairpins to favor monoU addition. Conversely, the switch to oligoU requires the ZK domain of Lin28 to drive the formation of a stable ternary complex between pre-let-7 and the inactive LIM. Finally, ZK2 of TUT4(7) aids oligoU addition by engaging the growing oligoU tail through uracil-specific interactions.

SUBMITTER: Faehnle CR

PROVIDER: S-EPMC5542866 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Multi-domain utilization by TUT4 and TUT7 in control of let-7 biogenesis.

Faehnle Christopher R CR Walleshauser Jack J Joshua-Tor Leemor L

Nature structural & molecular biology 20170703 8

The uridyl transferases TUT4 and TUT7 (collectively called TUT4(7)) switch between two modes of activity, either promoting expression of let-7 microRNA (monoU) or marking it for degradation (oligoU). Lin28 modulates the switch via recruitment of TUT4(7) to the precursor pre-let-7 in stem cells and human cancers. We found that TUT4(7) utilize two multidomain functional modules during the switch from monoU to oligoU. The catalytic module (CM) is essential for both activities, while the Lin28-inter ...[more]

PMID: 28671666

Similar Datasets

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

Project description: Not available

| S-EPMC4191393 | biostudies-literature

Uridylation by TUT4 and TUT7 marks mRNA for degradation.

Project description: Not available

| S-EPMC4720960 | biostudies-literature

Uridylation by TUT4 and TUT7 marks mRNA for degradation

Project description:This SuperSeries is composed of the SubSeries listed below.

2014-12-04 | GSE59628 | GEO

Uridylation by TUT4 and TUT7 marks mRNA for degradation [TAIL-Seq]

2014-12-04 | GSE59627 | GEO

Uridylation by TUT4 and TUT7 marks mRNA for degradation [RNA-Seq]

2014-12-04 | GSE59626 | GEO

Uridylation by TUT4 and TUT7 marks mRNA for degradation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-12-04 | E-GEOD-59628 | biostudies-arrayexpress

Uridylation by TUT4 and TUT7 marks mRNA for degradation [RNA-Seq]

Project description:Uridylation occurs pervasively on mRNAs in mammals, yet its mechanism and significance remain unknown. Here we identify TUT4 and TUT7 (also known as ZCCHC11 and ZCCHC6, respectively) as the enzymes that uridylate mRNAs. Uridylation readily occurs on deadenylated mRNAs that are not associated with poly(A) binding protein (PABPC1) in cells. Consistently, purified TUT4 and TUT7 (TUT4/7) selectively uridylate RNAs with short A tails (< ~25 nt) while PABPC1 antagonizes uridylation of polyadenylated mRNAs in vitro. In cells depleted of TUT4/7, the vast majority of mRNAs lose the U tails, and their half-lives are extended. Suppression of mRNA decay factors leads to the accumulation of uridylated mRNAs. In line with this, microRNA induces uridylation of its targets, and TUT4/7 is required for enhanced decay of microRNA targets. Our study explains the mechanism underlying selective uridylation of deadenylated mRNAs, and demonstrates a fundamental role of the U tail as a molecular mark for global mRNA decay. HeLa cells were knocked down of control or TUT4/7, then total RNAs were prepared for RNA-seq on 0, 1, 2, 4h after actinomycin D treatment. The whole processes of experiments were repeated two times.

2014-12-04 | E-GEOD-59626 | biostudies-arrayexpress

Uridylation by TUT4 and TUT7 marks mRNA for degradation [TAIL-Seq]

Project description:Uridylation occurs pervasively on mRNAs in mammals, yet its mechanism and significance remain unknown. Here we identify TUT4 and TUT7 (also known as ZCCHC11 and ZCCHC6, respectively) as the enzymes that uridylate mRNAs. Uridylation readily occurs on deadenylated mRNAs that are not associated with poly(A) binding protein (PABPC1) in cells. Consistently, purified TUT4 and TUT7 (TUT4/7) selectively uridylate RNAs with short A tails (< ~25 nt) while PABPC1 antagonizes uridylation of polyadenylated mRNAs in vitro. In cells depleted of TUT4/7, the vast majority of mRNAs lose the U tails, and their half-lives are extended. Suppression of mRNA decay factors leads to the accumulation of uridylated mRNAs. In line with this, microRNA induces uridylation of its targets, and TUT4/7 is required for enhanced decay of microRNA targets. Our study explains the mechanism underlying selective uridylation of deadenylated mRNAs, and demonstrates a fundamental role of the U tail as a molecular mark for global mRNA decay. Thirteen separate sets of TAIL-seq experiments were performed. Each set includes a negative control for transfection, immunoprecipitation, or knockout cell generation. Experimental samples were treated with various conditions including siRNA transfection, transdominant negative protein expression, TALEN-based gene knockout, or immunoprecipitation. The 'README-TAIL-seq.txt' include detailed information about structure of seq entries in FASTQ files and of processed data for 3' end modifications.

2014-12-04 | E-GEOD-59627 | biostudies-arrayexpress

Maternal mRNA degradation by TUT4 and TUT7 in the zebrafish maternal-to-zygotic transition

Project description:During the maternal-to-zygotic transition (MZT), maternal RNAs are actively degraded and replaced by newly-synthesized zygotic transcripts in a highly coordinated manner. However, it remains largely unknown how maternal mRNA decay is triggered in early vertebrate embryos. Here, through genome-wide profiling of RNA abundance and 3′ modification, we show that uridylation is induced at the onset of maternal mRNA clearance. The temporal control of uridylation is conserved in vertebrates. When the homologs of terminal uridylyltransferases TUT4 and TUT7 (TUT4/7) are depleted in zebrafish and Xenopus, maternal mRNA clearance is significantly delayed, leading to developmental defects during gastrulation. Short-tailed mRNAs are selectively uridylated by TUT4/7, with the highly uridylated transcripts degraded faster during the MZT than those with unmodified poly(A) tails. Our study demonstrates that uridylation plays a crucial role in timely mRNA degradation, thereby allowing the progression of early development.

2018-04-13 | GSE111152 | GEO

Small RNA profiling of TUT4 and TUT7-deficient mouse pachytene-diplotene cells.

Project description:To study the impact of TUT4 and TUT7 on miRNA and piRNA biology, Tut4 and Tut7 were conditionally deleted in differentiating spermatogonia. Total RNA samples from TUT4 and TUT7-deficient pachytene-diplotene cells were used to generate small RNAs libraries.

2019-01-14 | E-MTAB-7065 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data