ArticleNature2014
Mechanism of Dis3l2 substrate recognition in the Lin28-let-7 pathway.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 124 citations in OpenAlex.
- 40S ribosome remodeling triggers 18S rRNA U-tailing and DIS3L2-dependent decay.Molecular cell · 2026Article
- Oligo(uridine) tailing and exonucleolytic decay drive 40S ribosome degradation in response to stress.Molecular cell · 2026Article
- RNA-binding proteins in the mouse lens: Functional classifications, expression profiling, and interaction studies of Carhsp1 with crystallin mRNAs.Developmental biology · 2026Article
- LIN28A-Dependent Kinome and Phosphoproteome Reprogramming Promotes Imatinib Resistance.Molecular & cellular proteomics : MCP · 2026Article
- Mechanistic insights into Lin28-dependent oligo-uridylylation of pre-let-7 by TUT4.Nucleic acids research · 2026Article
- RNA Editors Sculpt the Transcriptome During Terminal Erythropoiesis.Research square · 2025Article
- Heterogeneous nuclear ribonucleoprotein C promotes non-small cell lung cancer progression by enhancing XB130 mRNA stability and translation.Cancer cell international · 2025Article
- RNA 3'end tailing safeguards cells against products of pervasive transcription termination.Nature communications · 2024Article
- Poly(U) polymerase activity in Caenorhabditis elegans regulates abundance and tailing of sRNA and mRNA.Genetics · 2024Article
- Structural basis for activity switching in polymerases determining the fate of let-7 pre-miRNAs.Nature structural & molecular biology · 2024Article
- LINE-1 mRNA 3' end dynamics shape its biology and retrotransposition potential.Nucleic acids research · 2024Article
- Article
- Conditional ablation of DIS3L2 ribonuclease in pre-meiotic germ cells causes defective spermatogenesis and infertility in male mice.Theranostics · 2024Article
- microRNAs in action: biogenesis, function and regulation.Nature reviews. Genetics · 2023Review
- An extensive survey of phytoviral RNA 3' uridylation identifies extreme variations and virus-specific patterns.Plant physiology · 2023Article
- DIS3L2 knockdown impairs key oncogenic properties of colorectal cancer cells via the mTOR signaling pathway.Cellular and molecular life sciences : CMLS · 2023Article
- How hydrolytic exoribonucleases impact human disease: Two sides of the same story.FEBS open bio · 2023Review
- DIS3L2 ribonuclease degrades terminal-uridylated RNA to ensure oocyte maturation and female fertility.Nucleic acids research · 2023Article
- A shape-shifting nuclease unravels structured RNA.Nature structural & molecular biology · 2023Article
- Trypanosoma brucei RRP44: a versatile enzyme for processing structured and non-structured RNA substrates.Nucleic acids research · 2023Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The pluripotency factor Lin28 inhibits the biogenesis of the let-7 family of mammalian microRNAs. Lin28 is highly expressed in embryonic stem cells and has a fundamental role in regulation of development, glucose metabolism and tissue regeneration. Overexpression of Lin28 is correlated with the onset of numerous cancers, whereas let-7, a tumour suppressor, silences several human oncogenes. Lin28 binds to precursor let-7 (pre-let-7) hairpins, triggering the 3' oligo-uridylation activity of TUT4 and TUT7 (refs 10-12). The oligoU tail added to pre-let-7 serves as a decay signal, as it is rapidly degraded by Dis3l2 (refs 13, 14), a homologue of the catalytic subunit of the RNA exosome. The molecular basis of Lin28-mediated recruitment of TUT4 and TUT7 to pre-let-7 and its subsequent degradation by Dis3l2 is largely unknown. To examine the mechanism of Dis3l2 substrate recognition we determined the structure of mouse Dis3l2 in complex with an oligoU RNA to mimic the uridylated tail of pre-let-7. Three RNA-binding domains form an open funnel on one face of the catalytic domain that allows RNA to navigate a path to the active site different from that of its exosome counterpart. The resulting path reveals an extensive network of uracil-specific interactions spanning the first 12 nucleotides of an oligoU-tailed RNA. We identify three U-specificity zones that explain how Dis3l2 recognizes, binds and processes uridylated pre-let-7 in the final step of the Lin28-let-7 pathway.
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Registered trials
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.