Affinage

DIS3L2

DIS3-like exonuclease 2 · UniProt Q8IYB7

Length
885 aa
Mass
99.3 kDa
Annotated
2026-06-09
38 papers in source corpus 24 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DIS3L2 is a cytoplasmic, exosome-independent 3'-5' exoribonuclease that defines a quality-control pathway in which substrates marked by 3'-oligouridylation are recognized and degraded (PMID:23503588, PMID:27647875). Its catalytic specificity arises from a distinctive architecture: three RNA-binding domains (two cold-shock domains and an S1 domain) form an open funnel that channels uridylated RNA into the RNB active site through U-specificity zones spanning the first ~12 nucleotides, a path structurally distinct from the exosome (PMID:25119025, PMID:26057668). Substrate selection is set upstream by the terminal uridyltransferases TUT4/TUT7 (ZCCHC11/ZCCHC6), which append the oligo(U) tags that stimulate DIS3L2 activity in vitro and in vivo (PMID:23594738, PMID:24141620). Through this TUT-DIS3L2 logic the enzyme degrades a broad spectrum of cytoplasmic RNAs: uridylated pre-let-7 in the LIN28-TUT4/7-DIS3L2 pathway (PMID:23594738, PMID:24141620), AGO-associated mature miRNAs with exposed 3' ends (PMID:32488030), aberrant structured noncoding RNAs including rRNAs, snRNAs, vault RNAs, Y RNAs, 7SL and Rmrp (PMID:27647875, PMID:27498873), NMD-targeted mRNAs in a UPF1- and TUTase-dependent manner (PMID:31466720), apoptotic mRNA decay intermediates (PMID:25959823), and uridylated-poly(A) mRNAs during oocyte maturation (PMID:36727488). Loss of DIS3L2 produces wide-ranging consequences: mitotic abnormalities and spindle defects (PMID:22306653, PMID:40500755), tissue overgrowth and proliferation driven by PI3K/AKT signaling and Igf2 upregulation (PMID:29950491, PMID:33370287), impaired ER-targeted translation and calcium signaling through failed 7SL quality control (PMID:32457326), innate immune activation by aberrant RNAs diverted into extracellular vesicles (PMID:41401009), and infertility from defective oocyte maturation and spermatogenesis in mice (PMID:36727488, PMID:39310107). DIS3L2 also has an exonuclease-independent role, binding hnRNP U through its cold-shock domains to promote oncogenic Rac1b alternative splicing (PMID:31331910).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2012 High

    Establishing that DIS3L2 is a distinct exoribonuclease answered whether it is simply another exosome-associated DIS3 paralog or an independent enzyme with its own cellular role.

    Evidence in vitro exonuclease assay, siRNA knockdown with mitotic readout, and subcellular localization in human cells

    PMID:22306653

    Open questions at the time
    • Substrate class not yet defined
    • Mechanism linking the enzyme to mitotic checkpoint proteins unresolved
  2. 2013 High

    Identification of uridylated pre-let-7 as a substrate placed DIS3L2 as the missing 3'-5' nuclease of the LIN28-TUT4/7-DIS3L2 axis, explaining how oligouridylation directs decay.

    Evidence biochemical reconstitution and RNA stability assays in mouse ES cells, plus RNA-IP and in vivo knockdown

    PMID:23594738 PMID:24141620

    Open questions at the time
    • Did not define the full substrate repertoire beyond pre-let-7
    • Structural basis of oligo(U) preference unknown
  3. 2013 High

    Showing in S. pombe that Dis3l2 acts in the cytoplasm independent of the exosome and is synthetically lethal with xrn1Δ established it as a self-contained alternative RNA degradation route.

    Evidence Co-IP showing non-interaction with exosome, microscopy at P-bodies, in vitro assay with uridylated substrates, and genetic epistasis

    PMID:23503588

    Open questions at the time
    • Conservation of exosome-independence to mammals not directly shown here
    • Physiological mRNA substrate set undefined
  4. 2014 High

    The crystal structure resolved how DIS3L2 achieves uridine specificity, answering how the catalytic mechanism differs from the exosome at atomic resolution.

    Evidence X-ray crystallography of mouse Dis3l2-oligoU complex with structure-function mutagenesis

    PMID:25119025

    Open questions at the time
    • Conformational dynamics during catalysis not captured
    • Recognition of structured vs single-stranded substrates not addressed
  5. 2015 High

    Crystallography of the S. pombe enzyme refined the model by showing a distinct conformation and assigning RNA-binding roles to individual domains, implying a conformational change on substrate engagement.

    Evidence X-ray crystallography with fluorescence polarization binding and domain mutagenesis

    PMID:26057668

    Open questions at the time
    • Direct visualization of the proposed conformational transition not obtained
    • Relevance to mammalian catalysis inferred
  6. 2015 High

    Linking DIS3L2 to apoptotic mRNA decay extended its role from noncoding RNA to programmed cell death, showing TUTase-marked truncated mRNA intermediates feed into the pathway.

    Evidence siRNA knockdown of DIS3L2 and TUTases with apoptotic readout, 3'-end sequencing, and overexpression assays

    PMID:25959823

    Open questions at the time
    • How apoptotic signaling routes mRNAs to TUTases unclear
    • Direct apoptotic substrates not individually validated
  7. 2016 High

    CLIP and reconstitution across mouse and human cells defined DIS3L2 as a quality-control nuclease for a broad class of aberrant uridylated structured ncRNAs, generalizing the TUT-DIS3L2 paradigm.

    Evidence in vivo CLIP, 3' RACE-Seq, global transcriptomics, biochemical reconstitution, and depletion across human and mouse cells

    PMID:27431325 PMID:27498873 PMID:27647875

    Open questions at the time
    • Functional consequence of failing to clear each ncRNA class not all defined
    • Determinants of which ncRNAs get uridylated unclear
  8. 2016 Medium

    Drosophila knockdown linked DIS3L2 loss to tissue overgrowth and revealed a compensatory relationship with the 5'-3' nuclease Pacman/Xrn1, framing opposing decay pathways in growth control.

    Evidence RNAi in wing discs, RNA-seq, and genetic epistasis with Pacman/Xrn1

    PMID:27630034

    Open questions at the time
    • Molecular target driving overgrowth not identified here
    • Compensation mechanism with Xrn1 not biochemically resolved
  9. 2018 Medium

    Demonstrating let-7-independent tumor suppression via Igf2 in nephron progenitors clarified that DIS3L2's growth-restraining function does not require miRNA regulation in all contexts.

    Evidence Dis3l2-null cells and mouse model with qRT-PCR (negative for let-7) and RNA-seq

    PMID:29950491

    Open questions at the time
    • Direct RNA substrate linking DIS3L2 to Igf2 not identified
    • Mechanism of Igf2 upregulation not resolved
  10. 2019 Medium

    An exonuclease-independent role in alternative splicing was uncovered, showing DIS3L2 can act as a protein scaffold recruiting hnRNP U, separating its catalytic and non-catalytic functions.

    Evidence reciprocal Co-IP, domain mapping, and splicing/functional assays

    PMID:31331910

    Open questions at the time
    • Generality of the scaffolding role beyond pre-Rac1 unknown
    • Single lab; structural basis of the cold-shock-domain/hnRNP U interaction undefined
  11. 2019 Medium

    Connecting DIS3L2 to a UPF1- and TUTase-dependent decay of NMD targets extended its substrate range to full-length mRNAs in surveillance pathways.

    Evidence siRNA knockdown of DIS3L2 and UPF1 with Northern blot, RT-qPCR, and reporter assays

    PMID:31466720

    Open questions at the time
    • Direct physical coupling to the UPF1/NMD machinery not shown
    • Which NMD targets are direct substrates not comprehensively defined
  12. 2020 High

    A triple-knockout dissection established the enzymatic order by which AGO mutations expose miRNA 3' ends, triggering TUT7-driven uridylation and DIS3L2 decay of mature miRNAs.

    Evidence genetic KO of TUT4, TUT7, and DIS3L2 in HEK293T with deep sequencing and AGO mutant analysis

    PMID:32488030

    Open questions at the time
    • Physiological trigger for AGO 3'-end exposure in wild-type cells unclear
    • Scope of miRNAs subject to this decay in vivo not defined
  13. 2020 High

    Defining 7SL quality control connected DIS3L2 to ER-targeted translation, showing how failed clearance of uridylated aberrant 7SL perturbs SRP function, calcium homeostasis, and differentiation.

    Evidence Ribo-seq, DIS3L2 KO in ESCs, calcium imaging, transcriptomics, and differentiation assays

    PMID:32457326

    Open questions at the time
    • Direct link between specific aberrant 7SL species and SRP assembly defects not fully resolved
    • Single lab
  14. 2020 Medium

    PI3K/AKT pathway activation was identified as a downstream effector of DIS3L2 loss in human cells and Drosophila, providing a signaling basis for the proliferation phenotype.

    Evidence DIS3L2 KO in human cells and Drosophila null mutant, Western blot, and PI3K/AKT inhibitor epistasis

    PMID:33370287

    Open questions at the time
    • RNA substrate upstream of AKT activation not identified
    • Direct vs indirect effect on the pathway not distinguished
  15. 2020 Medium

    Showing Sm-ring-deficient snRNAs accumulate in P-bodies, become uridylated, and associate with DIS3L2 in an LSm1-dependent, XRN1-competing manner refined the cellular logistics of structured-ncRNA surveillance.

    Evidence Co-IP, P-body microscopy, 3'-end sequencing, and XRN1-inhibition epistasis

    PMID:32374871

    Open questions at the time
    • Mechanism of LSm1-dependent P-body recruitment not resolved
    • Balance between DIS3L2 and XRN1 not quantitatively defined
  16. 2023 High

    A conditional oocyte knockout established a developmental requirement, showing DIS3L2 degrades uridylated-poly(A) mRNAs needed for proper meiotic maturation and female fertility.

    Evidence oocyte-specific Dis3l2 cKO with single-oocyte long-read PacBio RNA sequencing and transcriptome profiling

    PMID:36727488

    Open questions at the time
    • Identity of the critical maternal substrates not pinpointed
    • Coupling to maternal poly(A)-tail dynamics not mechanistically resolved
  17. 2024 Medium

    A pre-meiotic germ-cell knockout demonstrated a parallel requirement in spermatogenesis, linking DIS3L2-dependent RNA metabolism to meiotic progression and male fertility.

    Evidence Stra8-Cre conditional KO mouse with bulk RNA-seq and scRNA-seq

    PMID:39310107

    Open questions at the time
    • Direct germ-cell substrates not identified
    • Causal RNA targets driving meiotic arrest unknown
  18. 2025 High

    A vase-like structure with bound U13 RNA and a point mutant identified A756 as the residue enabling degradation of double-stranded/structured RNA, refining the catalytic mechanism for structured substrates.

    Evidence X-ray crystallography of SpDis3l2-U13 and in vitro assays with disease-mimicking point mutants

    PMID:41033841

    Open questions at the time
    • How the enzyme unwinds or accommodates duplex substrates not fully resolved
    • Mammalian equivalent of A756 not tested in cells
  19. 2025 Medium

    Showing DIS3L2 surveillance competes with extracellular-vesicle packaging of uridylated aberrant ncRNAs and prevents type I interferon activation linked the pathway to innate immune homeostasis.

    Evidence DIS3L2 depletion with EV purification, high-throughput RNA-seq, Northern blot, and ISG expression analysis

    PMID:41401009

    Open questions at the time
    • Sensor detecting the escaped aberrant RNAs not identified
    • Single lab
  20. 2025 Medium

    A zebrafish study tied dis3l2 to neural crest specification and early mitotic fidelity via Akt-GSK3β signaling, broadening its developmental roles.

    Evidence morpholino knockdown with immunofluorescence for mitotic markers and gene expression analysis

    PMID:40500755

    Open questions at the time
    • Morpholino specificity not orthogonally controlled
    • RNA substrates underlying neural crest and mitotic phenotypes unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • How DIS3L2 is recruited to and selects among its many substrate classes in vivo, and whether emerging roles as an i6A modification reader and a ZAP-mediated decay effector represent general mechanisms, remains unresolved.
  • i6A-reader claim is from a single unreviewed preprint
  • ZMD recruitment of DIS3L2 awaits peer-reviewed confirmation
  • No unifying model for substrate triage among competing decay pathways

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140098 catalytic activity, acting on RNA 6 GO:0003723 RNA binding 4 GO:0016787 hydrolase activity 4
Localization
GO:0005829 cytosol 3 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-8953854 Metabolism of RNA 4 R-HSA-168256 Immune System 1 R-HSA-5357801 Programmed Cell Death 1
Partners
AGOHNRNPUTUT4TUT7UPF1ZCCHC11ZCCHC6

Evidence

Reading pass · 26 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 DIS3L2 is the 3'-5' exonuclease responsible for the decay of uridylated pre-let-7 in mouse embryonic stem cells. Biochemical reconstitution assays demonstrated that 3' oligouridylation stimulates Dis3l2 activity in vitro, and knockdown of Dis3l2 in mouse embryonic stem cells leads to stabilization of pre-let-7. Biochemical reconstitution in vitro assay, siRNA knockdown in mouse embryonic stem cells, RNA stability assays Nature High 23594738
2012 DIS3L2 has exoribonuclease activity and a different intracellular localization from DIS3 and DIS3L1; it lacks the PIN domain. DIS3L2 inactivation was associated with mitotic abnormalities and altered expression of mitotic checkpoint proteins. In vitro exonuclease activity assay, siRNA knockdown with cell biological readout (mitotic abnormalities), subcellular localization by fractionation/imaging Nature genetics High 22306653
2013 In S. pombe, Dis3L2 defines a novel cytoplasmic 3'-5' RNA degradation pathway independent of the exosome. Dis3L2 does not interact with exosome components, localizes in the cytoplasm and in cytoplasmic foci docked to P-bodies, shows preference for uridylated substrates in vitro, and synthetic lethality with xrn1Δ indicates it provides an alternative mRNA degradation route. Co-immunoprecipitation (non-interaction with exosome), subcellular localization by microscopy, in vitro exonuclease assay with uridylated substrates, genetic epistasis (synthetic lethality with xrn1Δ and lsm1Δ), mRNA stability assays The EMBO journal High 23503588
2013 DIS3L2 is an oligo(U)-binding and processing exoribonuclease that specifically targets uridylated pre-let-7 in vivo, establishing it as the missing component of the LIN28-TUT4/7-DIS3L2 pathway for let-7 repression in pluripotent cells. RNA immunoprecipitation, in vivo knockdown with pre-let-7 stability assays, biochemical binding assays RNA (New York, N.Y.) High 24141620
2014 Crystal structure of mouse Dis3l2 in complex with oligoU RNA revealed that three RNA-binding domains (two CSDs and an S1 domain) form an open funnel on one face of the catalytic domain, creating a path to the active site distinct from the exosome. Three U-specificity zones spanning the first 12 nucleotides explain how Dis3l2 recognizes and processes uridylated pre-let-7. X-ray crystallography of Dis3l2-oligoU RNA complex, structure-function mutagenesis Nature High 25119025
2015 During apoptosis, 3' truncated mRNA decay intermediates with nontemplated uridylate-rich tails are generated by TUTases ZCCHC6/ZCCHC11 and are degraded by DIS3L2. Knockdown of DIS3L2 or TUTases inhibits apoptotic mRNA decay, translation arrest, and cell death, whereas DIS3L2 overexpression enhances cell death. siRNA knockdown of DIS3L2 and TUTases with apoptotic phenotype readout, 3'-end sequencing to detect uridylated intermediates, overexpression assays Cell reports High 25959823
2016 DIS3L2 degrades a broad spectrum of uridylated cytoplasmic structured noncoding RNAs (rRNAs, snRNAs, snoRNAs, tRNAs, vault RNAs, 7SL, Y RNAs) identified by in vivo CLIP. Most substrates have aberrant processing and stable secondary structures, establishing TUT-DIS3L2 as a cytoplasmic quality control pathway for structured ncRNAs. In vivo CLIP (cross-linking and immunoprecipitation), DIS3L2 depletion with RNA stabilization assays The EMBO journal High 27647875
2016 Dis3l2-mediated decay (DMD) targets uridylated ncRNAs including lncRNA Rmrp, 7SL, and snRNAs in mouse embryonic stem cells. TUTases Zcchc6/11 uridylate these substrates, and biochemical reconstitution assays demonstrate TUTase-Dis3l2 sufficiency for Rmrp decay. RNA immunoprecipitation, deep sequencing of 3' ends, siRNA knockdown, biochemical reconstitution assay Cell reports High 27498873
2016 DIS3L2 in human cells contributes to surveillance of maturing snRNAs during cytoplasmic processing. All novel DIS3L2 substrates (including vault RNAs, Y RNAs, BC200 RNA, snRNAs) are uridylated in vivo by TUT4/TUT7, and uridylation-dependent DIS3L2-mediated decay can be recapitulated in vitro. Global transcriptomics, 3' RACE-Seq, in vitro reconstitution assay, DIS3L2 depletion Nucleic acids research High 27431325
2016 Knockdown of dis3L2 in Drosophila wing imaginal discs results in wing overgrowth due to increased cellular proliferation. A compensatory relationship between Dis3L2 and 5'-3' exoribonuclease Pacman was demonstrated, indicating they regulate opposing degradation pathways. RNAi knockdown in Drosophila tissue, RNA-seq, genetic epistasis with Pacman/Xrn1 RNA biology Medium 27630034
2015 Crystal structure of S. pombe Dis3l2 (SpDis3l2) was solved at 2.8 Å. Fluorescence polarization assays showed RNB and S1 domains are primary RNA-binding domains, and CSD1/CSD2 play an indispensable role in RNA binding. The conformation differs from the mouse Dis3l2-RNA complex, suggesting a conformational change upon substrate binding. X-ray crystallography, fluorescence polarization binding assays, mutagenesis of RNA-binding domains Acta crystallographica. Section D, Biological crystallography High 26057668
2019 DIS3L2 directly interacted with hnRNP U through its cold-shock domains and promoted inclusion of exon 3b during splicing of pre-Rac1, independent of its exonuclease activity, yielding oncogenic Rac1b variant. DIS3L2 regulated alternative splicing by recruiting hnRNP U to pre-Rac1. Co-immunoprecipitation, splicing assays, domain mapping, in vitro and in vivo functional assays Cancer research Medium 31331910
2018 DIS3L2 loss in mouse nephron progenitor cells has no effect on mature let-7 levels but results in up-regulation of Igf2, a growth-promoting gene strongly associated with Wilms tumorigenesis, identifying a let-7-independent mechanism for DIS3L2-mediated tumor suppression. Dis3l2-null cell lines and mouse models, qRT-PCR for mature let-7 levels (negative finding for let-7), RNA-seq of nephron progenitor cells Genes & development Medium 29950491
2019 DIS3L2 regulates the levels of a subset of NMD-targeted mRNAs in human cells, acting over full-length transcripts through a process involving UPF1. DIS3L2-mediated decay of NMD targets is dependent on the activity of TUTases Zcchc6/11 (TUT7/4). siRNA knockdown of DIS3L2 and UPF1, Northern blot, RT-qPCR, reporter assays Biochemical and biophysical research communications Medium 31466720
2020 AGO mutations disrupting miRNA 3' binding trigger extensive miRNA 3' uridylation by TUT7 (more robustly than TUT4), which leads to degradation of AGO-associated mature miRNAs by DIS3L2, revealing a decay machinery targeting AGO-associated miRNAs with an exposed 3' end. Genetic KO of TUT4, TUT7, and DIS3L2 in HEK293T cells, deep sequencing, AGO mutant analysis Nature communications High 32488030
2020 DIS3L2-mediated decay (DMD) functions in the quality control of the 7SL ncRNA component of the signal recognition particle (SRP). Upon DIS3L2 loss, sustained 3'-end uridylation of aberrant 7SL RNA impairs ER-targeted translation and causes ER calcium leakage, activating calcium signaling response genes and perturbing ESC differentiation. Ribosome profiling (Ribo-seq), DIS3L2 KO in ESCs, calcium imaging, transcriptomics, functional differentiation assays Nature communications High 32457326
2020 Dis3L2 loss results in upregulation of the PI3-Kinase/AKT signaling pathway in human HEK-293T cells, and this pathway contributes to the proliferation phenotype caused by DIS3L2 loss both in human cells and in Drosophila. DIS3L2 KO in human cells plus Drosophila null mutant; Western blot for AKT pathway; epistasis with PI3K/AKT inhibitors in Drosophila PLoS genetics Medium 33370287
2020 Sm ring-deficient snRNAs accumulate in P-bodies in an LSm1-dependent manner, are uridylated at the 3' end, and associate with DIS3L2. Inhibition of XRN1 increases association of defective snRNAs with DIS3L2, indicating competition and compensation between DIS3L2 and XRN1 in degradation of aberrant snRNAs. Co-immunoprecipitation, fluorescence microscopy (P-body localization), 3' end sequencing, XRN1 inhibition epistasis Nucleic acids research Medium 32374871
2023 DIS3L2 ribonuclease is required for degradation of uridylated-poly(A) mRNAs during oocyte maturation in mice. Oocyte-specific Dis3l2 knockout causes arrest at the germinal vesicle stage, female infertility, and accumulation of uridylated-poly(A) RNAs with shorter poly(A) tails and decreased translation. Conditional KO mouse model (Dis3l2cKO), single-oocyte long-read PacBio RNA sequencing, transcriptome profiling Nucleic acids research High 36727488
2025 Crystal structure of SpDis3l2 bound to U13 RNA in a vase-like conformation accommodating 6 nucleotides. The A756R variant loses the ability to degrade double-stranded RNA substrates and accumulates intermediate products on single-stranded RNA, identifying A756 as a key residue for degradation of structured RNA substrates. X-ray crystallography, in vitro biochemical assays with disease-mimicking point mutants RNA (New York, N.Y.) High 41033841
2024 Conditional ablation of Dis3l2 in pre-meiotic germ cells impairs spermatogonial differentiation and hinders spermatocyte meiotic progression coupled with apoptosis, causing defective spermatogenesis and male infertility, associated with disrupted RNA metabolism and downregulation of cell cycle and meiotic genes. Conditional KO mouse model (Stra8-Cre), bulk RNA-seq, scRNA-seq Theranostics Medium 39310107
2025 DIS3L2 surveillance and EV packaging of uridylated aberrant ncRNAs are competing pathways; DIS3L2 depletion increases EV release and fractions of tailed RNAs in EVs, and upregulates type I interferon-stimulated genes (ISGs), indicating DIS3L2-mediated decay prevents innate immune activation by aberrant cellular RNAs. DIS3L2 depletion, EV purification and high-throughput RNA sequencing, Northern blotting, ISG expression analysis Proceedings of the National Academy of Sciences of the United States of America Medium 41401009
2025 In the ZAP-mediated RNA decay (ZMD) pathway, ZAP and TRIM25 recruit DIS3L2 along with TUT4/TUT7 and other enzymes; after KHNYN endonucleolytic cleavage, the 5' cleavage fragment undergoes TUT4/TUT7-mediated 3' uridylation and is then degraded by DIS3L2. Co-immunoprecipitation (RNase-resistant interactions), KO cell lines, RNA decay assays bioRxivpreprint Medium
2025 DIS3L2 was identified as the first i6A (N6-isopentenyladenosine) reader protein. i6A modification in mRNA CDS regions of ER-bound transcripts promotes their decay via DIS3L2, identifying i6A as a new mRNA modification that regulates gene expression through DIS3L2-mediated mRNA decay. i6A-seq transcriptome mapping, TRIT1 manipulation, DIS3L2 KD/KO with mRNA stability assays bioRxivpreprint Low
2025 In zebrafish embryos, dis3l2 regulates neural crest specification and survival through the Akt-GSK3β signaling pathway. dis3l2 morphants show reduced neural crest specifier gene expression and extensive apoptosis in neural tissue. Dis3l2 is also essential for early mitoses, maintaining spindle length, chromosome congression, spindle pole integrity, and cytokinesis. Morpholino knockdown in zebrafish, immunofluorescence for mitotic markers, gene expression analysis Cell communication and signaling : CCS Medium 40500755
2025 hnRNPR protects XB130 mRNA from DIS3L2-mediated degradation by binding to specific regions within the XB130 3'UTR, indicating that DIS3L2 can be antagonized by RNA-binding proteins through 3'UTR competition. RNA pull-down, RNA immunoprecipitation, mRNA stability assays, dual-luciferase reporter assay Cellular signalling Low 40268079

Source papers

Stage 0 corpus · 38 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway. Nature 274 23594738
2012 Germline mutations in DIS3L2 cause the Perlman syndrome of overgrowth and Wilms tumor susceptibility. Nature genetics 187 22306653
2013 The exoribonuclease Dis3L2 defines a novel eukaryotic RNA degradation pathway. The EMBO journal 171 23503588
2013 Mammalian DIS3L2 exoribonuclease targets the uridylated precursors of let-7 miRNAs. RNA (New York, N.Y.) 147 24141620
2015 Apoptosis Triggers Specific, Rapid, and Global mRNA Decay with 3' Uridylated Intermediates Degraded by DIS3L2. Cell reports 122 25959823
2014 Mechanism of Dis3l2 substrate recognition in the Lin28-let-7 pathway. Nature 112 25119025
2016 TUT-DIS3L2 is a mammalian surveillance pathway for aberrant structured non-coding RNAs. The EMBO journal 92 27647875
2016 Perlman syndrome nuclease DIS3L2 controls cytoplasmic non-coding RNAs and provides surveillance pathway for maturing snRNAs. Nucleic acids research 75 27431325
2016 Dis3l2-Mediated Decay Is a Quality Control Pathway for Noncoding RNAs. Cell reports 75 27498873
2020 AGO-bound mature miRNAs are oligouridylated by TUTs and subsequently degraded by DIS3L2. Nature communications 64 32488030
2019 DIS3L2 Promotes Progression of Hepatocellular Carcinoma via hnRNP U-Mediated Alternative Splicing. Cancer research 40 31331910
2018 Loss of Dis3l2 partially phenocopies Perlman syndrome in mice and results in up-regulation of Igf2 in nephron progenitor cells. Genes & development 35 29950491
2013 Perlman syndrome: overgrowth, Wilms tumor predisposition and DIS3L2. American journal of medical genetics. Part C, Seminars in medical genetics 35 23613427
2016 The roles of the exoribonucleases DIS3L2 and XRN1 in human disease. Biochemical Society transactions 28 27911720
2013 Homozygous deletion of DIS3L2 exon 9 due to non-allelic homologous recombination between LINE-1s in a Japanese patient with Perlman syndrome. European journal of human genetics : EJHG 20 23486540
2016 A novel role for the 3'-5' exoribonuclease Dis3L2 in controlling cell proliferation and tissue growth. RNA biology 19 27630034
2020 The Perlman syndrome DIS3L2 exoribonuclease safeguards endoplasmic reticulum-targeted mRNA translation and calcium ion homeostasis. Nature communications 17 32457326
2020 DIS3L2 and LSm proteins are involved in the surveillance of Sm ring-deficient snRNAs. Nucleic acids research 16 32374871
2020 Dis3L2 regulates cell proliferation and tissue growth through a conserved mechanism. PLoS genetics 16 33370287
2019 A role for DIS3L2 over natural nonsense-mediated mRNA decay targets in human cells. Biochemical and biophysical research communications 13 31466720
2017 Knockdown of a DIS3L2 promoter upstream long noncoding RNA (AC105461.1) enhances colorectal cancer stem cell properties in vitro by down-regulating DIS3L2. OncoTargets and therapy 12 28496335
2023 DIS3L2 ribonuclease degrades terminal-uridylated RNA to ensure oocyte maturation and female fertility. Nucleic acids research 11 36727488
2019 Regulation of RNA decay and cellular function by 3'-5' exoribonuclease DIS3L2. RNA biology 11 30638126
2017 Immunohistochemical localization of exoribonucleases (DIS3L2 and XRN1) in intranuclear inclusion body disease. Neuroscience letters 11 29100804
2015 Structural analysis of Dis3l2, an exosome-independent exonuclease from Schizosaccharomyces pombe. Acta crystallographica. Section D, Biological crystallography 10 26057668
2017 Long term survival of a patient with Perlman syndrome due to novel compound heterozygous missense mutations in RNB domain of DIS3L2. American journal of medical genetics. Part A 9 28328139
2024 Conditional ablation of DIS3L2 ribonuclease in pre-meiotic germ cells causes defective spermatogenesis and infertility in male mice. Theranostics 8 39310107
2022 Case Report: 2-Year-old With Wilms Tumors, Familial Heterozygous DIS3L2 Mutation, and Cutis Marmorata Telangiectatica Congenita. Journal of pediatric hematology/oncology 6 35700413
2023 DIS3L2 knockdown impairs key oncogenic properties of colorectal cancer cells via the mTOR signaling pathway. Cellular and molecular life sciences : CMLS 4 37340282
2019 Experimental supporting data on DIS3L2 over nonsense-mediated mRNA decay targets in human cells. Data in brief 2 31886366
2025 Structural and mechanistic insights into Dis3L2-mediated degradation of structured RNA. RNA (New York, N.Y.) 1 41033841
2025 DIS3L2-mediated RNA surveillance and extracellular vesicle packaging prevent innate immune activation by aberrant cellular RNAs. Proceedings of the National Academy of Sciences of the United States of America 1 41401009
2023 DIS3L2 Gene Mutation Causes the Perlman Syndrome of Overgrowth and Wilms Tumor Susceptibility. Cureus 1 38161545
2022 [Clinical features and genetic analysis of a case with Perlman syndrome due to variant of DIS3L2 gene]. Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics 1 34964966
2026 Investigation of the Relationship Between Ovine Selection Signature DIS3 Like 3'-5' Exoribonuclease 2 (DIS3L2) Gene and Weaning Weight and Average Daily Gain Until Weaning in Lambs. Animal genetics 0 42229879
2025 HnRNPR promotes non-small cell lung cancer progression by protecting XB130 mRNA from XRN1- and DIS3L2-mediated degradation. Cellular signalling 0 40268079
2025 Dis3l2 is essential for neural crest survival by modulating Akt signaling. Cell communication and signaling : CCS 0 40500755
2025 Phenotypic Carney-Stratakis syndrome with DIS3L2 variant: a case challenging the current genetic paradigm. Proceedings (Baylor University. Medical Center) 0 41341087

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