Affinage

MSI2

RNA-binding protein Musashi homolog 2 · UniProt Q96DH6

Length
328 aa
Mass
35.2 kDa
Annotated
2026-06-10
91 papers in source corpus 43 papers cited in narrative 42 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

MSI2 is an RNA-binding protein bearing two RNA recognition motifs that controls cell fate post-transcriptionally by recognizing UAG/UUAG motifs concentrated in 3'UTRs and IRES elements of target mRNAs (PMID:12649177, PMID:30126842, PMID:35528200). It maintains stem and progenitor cell self-renewal: depletion impairs hematopoietic stem cell repopulation and drives differentiation, whereas overexpression enhances self-renewal (PMID:20621054), and it sustains both normal and malignant hematopoietic and progenitor populations in MDS, AML, and other tissues (PMID:26898884, PMID:33623142). Mechanistically MSI2 binds thousands of transcripts but exerts functional translational repression on a high-density subset, with EIF3A as an immediate translational target (PMID:35528200); it represses tumour-suppressor mRNAs such as Lrig1, Pten, Cdkn1a and NUMB to drive Wnt-independent, PDK-AKT-mTORC1-dependent oncogenic programs (PMID:25774828, PMID:38847273), and post-transcriptionally promotes oncogenic outputs by enhancing translation or stability of FLT3, EGFR, TGFβR1/SMAD3, NLK, and MYC, the latter through IRES-dependent and m6A-dependent mechanisms (PMID:27274057, PMID:28107692, PMID:33723247, PMID:35073459, PMID:37117191, PMID:39097735). MSI2 operates within RBP networks, interacting with SYNCRIP to maintain HOXA9 translation and leukemia (PMID:28436985), with LIN28 (via a CSD–RRM contact) to degrade Hippo-pathway kinase mRNAs and activate YAP1 (PMID:35102250), and with HuR to control miRNA processing during myogenesis (PMID:34877814). MSI2 abundance and localization are tightly regulated: it is transcriptionally controlled by KLF4, ETV4, HMGA2, C/EBPα p30, and FOXF2 (PMID:27449499, PMID:31253395, PMID:31053152, PMID:33623142, PMID:38847273), stabilized against SCFβ-TRCP-mediated ubiquitination (PMID:35073459), and partitioned between cytoplasmic translation-promoting and nuclear/chromatin-associated roles by importin-7-dependent nuclear import and alternative splicing of distinct isoforms (PMID:42066897, PMID:42239307). Beyond cancer, MSI2 supports photoreceptor alternative splicing and survival, muscle stem cell differentiation through autophagy, and ovarian follicle development (PMID:33168629, PMID:38373797, PMID:26131972). A germline non-coding variant lowering HSC-selective MSI2 expression protects against clonal hematopoiesis and myeloid malignancy, defining MSI2 as a modifier of human HSC fitness [PMID:bio_10.1101_2025.03.24.645017].

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2003 Medium

    Establishing that MSI2 is a two-RRM RNA-binding protein and recurrently rearranged in CML progression first linked the gene to both RNA biology and leukemia.

    Evidence Molecular cloning and breakpoint sequencing of a t(7;17) MSI2/HOXA9 fusion in CML

    PMID:12649177

    Open questions at the time
    • Did not establish the normal function of MSI2 or its RNA targets
    • Functional consequence of the fusion protein untested
  2. 2010 High

    Reciprocal loss- and gain-of-function in vivo answered whether MSI2 has a cell-fate role, defining it as a positive regulator of hematopoietic stem cell self-renewal.

    Evidence In vivo RNAi screen, shRNA/overexpression and competitive repopulation in mouse HSCs

    PMID:20621054

    Open questions at the time
    • Direct mRNA targets in HSCs not mapped
    • Mechanism of repression not resolved
  3. 2015 High

    Transcriptome-wide CLIP plus in vivo gain-of-function and pharmacological epistasis showed MSI2 acts as a pleiotropic repressor of tumour suppressors driving oncogenesis through PDK-AKT-mTORC1.

    Evidence Drug-inducible mouse overexpression, PAR-CLIP/CLIP, pharmacological rescue in intestine

    PMID:25774828

    Open questions at the time
    • Whether repression is via decay or translation per target unclear
    • Wnt-independence mechanism not fully dissected
  4. 2016 High

    Cell-line and in vivo studies extended MSI2 to solid-tumour metastasis and to maintaining malignant hematopoiesis, showing it translationally supports TGFβ signaling and is required for MDS HSPCs.

    Evidence shRNA/rescue invasion and metastasis assays (NSCLC); conditional KO and inducible OE mouse MDS models

    PMID:26898884 PMID:27274057

    Open questions at the time
    • Direct binding sites on TGFβR1/SMAD3 not nucleotide-mapped
    • MDS-specific target program not defined
  5. 2017 High

    Proteomic and RIP studies placed MSI2 in cooperative RBP networks and identified direct oncogenic targets, showing MSI2 partners with SYNCRIP to maintain HOXA9 translation and binds FLT3 mRNA, and represses Hedgehog to keep stem cells quiescent.

    Evidence MS interactome, in vivo shRNA screen, RIP, gain/loss-of-function mouse models

    PMID:28107692 PMID:28143780 PMID:28436985

    Open questions at the time
    • Stoichiometry and architecture of the MSI2-SYNCRIP complex unknown
    • FLT3 binding shown by RIP without nucleotide-resolution mapping
  6. 2018 High

    Nucleotide-resolution crosslinking defined the UUAG recognition element and demonstrated MSI2 can drive target mRNA degradation, exemplified by IL6ST control of IL-6/STAT3 signaling.

    Evidence PAR-CLIP with MEME motif analysis, knockdown, phospho-Western in leukemia cells

    PMID:30126842

    Open questions at the time
    • Determinants choosing decay vs translational repression not resolved
  7. 2019 Medium

    Promoter-binding studies established that MSI2 expression is set by specific transcription factors and that MSI2 engages autophagy machinery, identifying KLF4 as a repressor, ETV4 and HMGA2 as activators, and Beclin1 as an interactor.

    Evidence ChIP, luciferase reporters, Co-IP, ChIP-seq, functional rescue and xenografts

    PMID:27449499 PMID:31053152 PMID:31253395

    Open questions at the time
    • Direct vs indirect contributions to autophagy unclear
    • Combinatorial regulation of the MSI2 promoter not integrated
  8. 2020 Medium

    Isoform-resolved and protein-interaction work showed MSI2 functions are context- and isoform-dependent, with MSI2a stabilizing TP53INP1 to restrain invasion and MSI2 controlling CAV1 protein stability.

    Evidence RIP, 3'UTR luciferase, isoform-specific assays, Co-IP and ubiquitylation assays

    PMID:32448269 PMID:32606289

    Open questions at the time
    • Mechanism by which MSI2 controls CAV1 ubiquitylation not defined
    • Isoform-specific binding determinants not mapped
  9. 2021 High

    Genetic and multi-omic studies broadened MSI2 into alternative splicing, miRNA processing, and non-hematopoietic stem cell biology, showing roles in photoreceptor exon usage, muscle stem cell differentiation, myofibroblast cytokine secretion, and C/EBPα-p30-driven AML.

    Evidence Conditional double KO retina, MSI2/HuR pri-miRNA processing in muscle stem cells, myofibroblast Col1a1-CreER KO, ATAC/ChIP/RNA-seq with CRISPR KO in AML

    PMID:33168629 PMID:33609283 PMID:33623142 PMID:34877814

    Open questions at the time
    • Whether splicing roles reflect direct nuclear MSI2 activity unclear
    • Tissue-specific target sets only partly defined
  10. 2022 High

    Integrated iCLIP/polysome and stability studies refined the model that MSI2 binds broadly but represses a high-density subset, while protein-stability and partner studies showed MSI2 is itself regulated by ubiquitination and recruited by LIN28.

    Evidence iCLIP with polysome profiling and acute depletion; Co-IP/ubiquitination assays; LIN28 CSD–RRM domain mapping and RIP

    PMID:35073459 PMID:35102250 PMID:35528200

    Open questions at the time
    • Rules determining functional vs non-functional binding incomplete
    • m6A-reader activity needs independent structural confirmation
  11. 2023 Medium

    Target-specific studies expanded MSI2's regulatory repertoire to IRES-dependent translation, lipid metabolism, and NLK-driven invasion, showing it enhances cap-independent translation of MYC/JUN/VEGFA and represses FASN.

    Evidence RIP-seq, IRES reporter assays, fatty acid profiling, defined mRNA binding sites with in vivo metastasis models

    PMID:37117191 PMID:38059915 PMID:39097735

    Open questions at the time
    • IRES targets identified by RIP without structural binding confirmation
    • Generality of IRES mechanism across targets unclear
  12. 2024 Medium

    Functional studies tied MSI2 to therapy resistance and additional biology, showing it controls ATM translation and DDR/PARP-inhibitor sensitivity, drives MYC-dependent chemoresistance in T-ALL, and supports muscle differentiation via autophagy.

    Evidence RIP, KP/KPM2 and Msi2-KO mouse models, single-cell RNA/TCR-seq of relapse pairs, autophagy rescue in myoblasts

    PMID:37398283 PMID:37801708 PMID:38373797 PMID:38659828

    Open questions at the time
    • Direct vs indirect link between MSI2 and ATM/autophagy not fully separated
    • miRNA/AGO2 recruitment role still emerging
  13. 2025 Medium

    Localization, interaction, and human genetic studies established how MSI2 is partitioned and how its dose matters, showing IPO7-mediated nuclear import forming an MSI2-MYC complex, β-catenin/LEF1 coupling, and a protective germline variant lowering HSC MSI2.

    Evidence Co-IP, NLS mutagenesis, fractionation, RIP/CLIP, TCF/LEF reporters, population genetics with ASXL1-mutant HSC competition

    PMID:40301545 PMID:42066897 PMID:bio_10.1101_2025.03.24.645017

    Open questions at the time
    • Causal target driving the protective variant's effect not pinned
    • Nuclear MSI2 functional repertoire incompletely defined
  14. 2026 Medium

    Isoform-resolved reconstitution distinguished cytoplasmic translation-promoting from nuclear chromatin-associated MSI2 activities, mapping localization signals and distinct interactomes.

    Evidence Tethered reporter assay, truncation/point mutagenesis, fractionation imaging, Co-IP/proteomics (preprint)

    PMID:42239307

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • Physiological balance of isoforms across tissues unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what structural and sequence features partition MSI2 binding into productive translational repression, activation, mRNA decay, m6A reading, and miRNA-processing outcomes across tissues.
  • No unifying rule linking binding density/site to regulatory outcome
  • No high-resolution structure of MSI2 in functional complexes (SYNCRIP, LIN28, IPO7-MYC)
  • Isoform abundance and switching in vivo not quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003723 RNA binding 5 GO:0045182 translation regulator activity 4 GO:0060090 molecular adaptor activity 4 GO:0140098 catalytic activity, acting on RNA 3
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953854 Metabolism of RNA 3
Partners
AGO2BECLIN1CAV1CTNNB1HURIPO7LIN28SYNCRIP

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 MSI2 encodes an RNA-binding protein with two RNA recognition motif (RRM) domains; a chromosomal translocation t(7;17)(p15;q23) creates an in-frame MSI2/HOXA9 fusion transcript retaining both RRM domains of MSI2 fused to the homeobox domain of HOXA9, identified at disease progression of CML. Molecular cloning, RT-PCR, sequence analysis of translocation breakpoints Cancer research Medium 12649177
2010 Msi2 shRNA-mediated depletion in mouse HSCs significantly impaired hematopoietic stem cell repopulation in vivo and promoted differentiation in vitro; conversely, Msi2 overexpression enhanced HSC self-renewal, establishing MSI2 as a positive regulator of HSC self-renewal. In vivo RNAi screen, shRNA knockdown, retroviral overexpression, competitive repopulation assays, gene expression profiling Cell stem cell High 20621054
2015 MSI2 acts as a pleiotropic post-transcriptional repressor of intestinal tumour suppressors including Lrig1, Bmpr1a, Cdkn1a, and Pten; MSI2 gain-of-function in intestinal epithelium phenocopied APC loss in a Wnt-independent manner, and PDK-AKT-mTORC1 inhibition rescued its oncogenic effects. Drug-inducible mouse overexpression model, transcriptome-wide RNA-binding analysis (PAR-CLIP/CLIP), loss-of-function experiments, pharmacological rescue Nature communications High 25774828
2016 MSI2 directly regulates translation of TGFβR1 and SMAD3 mRNAs to support TGF-β signaling and promote NSCLC metastasis; MSI2 depletion induced claudin tight-junction proteins (CLDN3, CLDN5, CLDN7) and overexpression of TGFβRI rescued the invasion deficit caused by MSI2 loss. shRNA depletion in multiple cell lines, rescue overexpression, invasion/metastasis assays in vitro and in vivo, Western blot, gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 27274057
2016 MSI2 expression is required for maintaining activated MDS hematopoietic stem and progenitor cells; conditional Msi2 deletion in a mouse MDS model caused rapid loss of MDS HSPCs and reversed clinical MDS features, while inducible MSI2 overexpression drove myeloid disease progression. Conditional knockout mouse, inducible overexpression mouse, flow cytometry, gene expression profiling Nature communications High 26898884
2017 MSI2 physically interacts with SYNCRIP (and other RBPs) through shared mRNA targets; proteomic analysis of the MSI2-interacting RBP network identified SYNCRIP as required for in vivo leukemia; SYNCRIP maintains HOXA9 translation and MSI2 or HOXA9 overexpression rescued SYNCRIP depletion effects. Proteomic interactome analysis (mass spectrometry), shRNA functional screen, gene expression profiling, rescue overexpression, in vivo leukemia assays Nature genetics High 28436985
2017 MSI2 protein directly binds FLT3 mRNA transcripts as shown by RNA immunoprecipitation; MSI2 loss leads to downregulation of FLT3 receptor expression in AML and CML blast crisis cells and impairs clonogenic growth, establishing post-transcriptional regulation of FLT3 by MSI2. RNA immunoprecipitation (RIP), shRNA knockdown, Western blot, clonogenic assay Leukemia research Medium 28107692
2017 MSI2 maintains quiescence of hair follicle stem cells by directly repressing Hedgehog signaling; Shh is a direct MSI2 target in hair follicle; forced MSI2 expression retards anagen entry and delays hair growth, while Msi2 loss enhances hair regrowth. Gain- and loss-of-function mouse models, unbiased transcriptome profiling, in vivo hair cycle analysis The Journal of investigative dermatology Medium 28143780
2018 PAR-CLIP identified MSI2's consensus RNA recognition element as the UUAG motif; MSI2 binds IL6ST (GP130) mRNA and promotes its degradation, thereby controlling IL-6/STAT3 and ERK signaling in leukemia cells. PAR-CLIP (photoactivatable ribonucleoside cross-linking and immunoprecipitation), MEME motif analysis, MSI2 knockdown, phospho-Western blot The Journal of biological chemistry High 30126842
2019 KLF4 directly binds the MSI2 promoter and transcriptionally represses MSI2 expression in pancreatic cancer cells; loss of KLF4 leads to MSI2 overexpression promoting PDAC proliferation, migration and metastasis. Chromatin immunoprecipitation (ChIP), luciferase reporter assay, gain- and loss-of-function experiments in vitro and in vivo Clinical cancer research Medium 27449499
2019 ETV4 directly binds the MSI2 promoter and transcriptionally upregulates MSI2 expression in lung adenocarcinoma; ectopic MSI2 expression rescues the inhibitory effects of ETV4 knockdown on LUAD proliferation and invasion. ChIP, luciferase reporter assay, CCK8/invasion assays, rescue overexpression Biochemical and biophysical research communications Medium 31253395
2019 MSI2 interacts with Beclin1 protein; MSI2 is transcriptionally activated by HMGA2 binding to the MSI2 promoter (ChIP-seq evidence); MSI2 overexpression reverses autophagy and growth defects caused by HMGA2 knockdown in NF1-MPNST cells. Co-immunoprecipitation, ChIP-seq, RNA-seq, functional rescue, xenograft Journal of experimental & clinical cancer research Medium 31053152
2020 MSI2 protein directly interacts with caveolin-1 (CAV1) in NF1-MPNST cells; MSI2 knockdown induces CAV1 protein expression by inhibiting its ubiquitylation, and CAV1 mediates the suppressive function of MSI2 knockdown on EMT, migration, invasion, and metastasis. Co-immunoprecipitation, ubiquitylation assay, shRNA knockdown, in vitro/in vivo metastasis assays Cell death & disease Medium 32606289
2020 MSI2a isoform (but not MSI2b) promotes TP53INP1 mRNA stability by interacting with the 3'-UTR of TP53INP1 mRNA; MSI2a expression inhibits TNBC cell invasion via TP53INP1-mediated suppression of ERK1/2 activity. RNA immunoprecipitation (RIP), RNA sequencing, luciferase assay, invasion assays, ERK inhibition Journal of experimental & clinical cancer research Medium 32448269
2021 MSI2 directly binds EGFR mRNA (demonstrated by RNA immunoprecipitation) and post-transcriptionally controls EGFR protein expression; MSI2 depletion reduces EGFR protein but not mRNA levels, and sensitizes EGFRmut NSCLC cells to EGFR inhibitors. RNA immunoprecipitation, RT-PCR, Western blot, RPPA, xenograft, cell line panel Oncogenesis Medium 33723247
2021 Loss of MSI1 and MSI2 together in photoreceptor neurons prevented use of photoreceptor-specific alternative exons in transcripts critical for outer segment morphogenesis, ciliogenesis, and synaptic transmission, causing photoreceptor degeneration; MSI2 alone is robustly expressed in adult retina and required for photoreceptor function. Conditional double KO mouse (pan-retinal and rod-specific), light response assay, immunohistochemistry, alternative splicing analysis The Journal of biological chemistry High 33168629
2021 MSI2 is required for myofibroblast-derived IL-6 and IL-11 secretion via the ERK1/2 pathway; conditional deletion of Msi2 in myofibroblasts inhibited orthotopic HCC growth and reduced metastasis in mice. Conditional KO mouse (Col1a1-CreER), orthotopic tumor transplantation, in vitro cytokine measurement, ERK pathway analysis Hepatology Medium 33609283
2021 MSI2 is identified as a critical effector gene downstream of C/EBPα p30 oncogene in CEBPA-mutated AML; p30 drives MSI2 expression through p30-dependent regulatory elements; MSI2 CRISPR knockout caused proliferation arrest, terminal myeloid differentiation, and delayed leukemia in vivo. ATAC-seq, ChIP-seq, RNA-seq, CRISPR/Cas9 KO, in vivo leukemia model Leukemia High 33623142
2021 MSI2 and HuR cooperatively bind pri-MiR7a-1 and repress its processing in an MSI2 dose-dependent manner; this promotes Cry2 translation (a miR-7a-1 target) and facilitates muscle stem cell differentiation and myogenesis. Immunoprecipitation followed by mass spectrometry, RNA immunoprecipitation, EMSA, luciferase assay, RNAi/overexpression in muscle stem cells, Msi2 KO mice Journal of cachexia, sarcopenia and muscle High 34877814
2022 iCLIP identified MSI2 binds thousands of mRNAs predominantly in 3'UTRs via UAG motifs; functional translational repression is restricted to a small subset bound at higher density with more UAG motifs; EIF3A is identified as an immediate direct translational target of MSI2. iCLIP (individual nucleotide resolution CLIP), polysome profiling, acute MSI2 depletion, complementary binding/expression analyses NAR cancer High 35528200
2022 LNC942 (LINC00942) prevents MSI2 interaction with SCFβ-TRCP E3 ubiquitin ligase, thereby inhibiting MSI2 ubiquitination and stabilizing MSI2 protein; stabilized MSI2 then promotes c-Myc mRNA stability in an m6A-dependent manner as an m6A reader protein. Co-immunoprecipitation, ubiquitination assay, RNA immunoprecipitation, RNA pull-down, human proteome array Clinical and translational medicine Medium 35073459
2022 LIN28 recruits MSI2 via LIN28 CSD domain interacting with MSI2 RRM domain; the LIN28/MSI2 complex promotes mRNA decay of YAP1 upstream kinases (MST1/2, LATS1/2), leading to YAP1 activation and cancer stem cell properties in TNBC. Co-immunoprecipitation, domain mapping, RNA immunoprecipitation, transcriptome analysis, in vitro and in vivo functional assays Oncogene Medium 35102250
2023 MSI2 binds the IRES of MYC, JUN, and VEGFA mRNAs and HCV IRES to increase their cap-independent (IRES-dependent) translation and promote tumor-initiating stem cell self-renewal; MSI2 also binds a lncRNA that interferes with miRNA processing to upregulate MYC translation. RIP-seq with anti-MSI2 antibody, IRES-reporter assays, MSI2 overexpression/inhibition, HCV replication assays in humanized mice Cell death discovery Medium 37117191
2023 MSI2 directly binds the 3'UTR of FASN mRNA (shown by RNA immunoprecipitation) and negatively regulates FASN expression, thereby decreasing unsaturated fatty acid content and triglyceride accumulation in bovine mammary epithelial cells. RNA immunoprecipitation, MSI2 knockdown, fatty acid profiling, Western blot Journal of agricultural and food chemistry Medium 38059915
2023 MSI2 directly binds to the translation regulatory region of NLK mRNA (positions 79-87 nt) to enhance its transcriptional activity and post-transcriptionally upregulate NLK; MSI2-NLK axis regulates EMT and PI3K-AKT-mTOR pathway to promote pancreatic cancer invasion, migration, and liver metastasis. Molecular docking, mRNA binding assays, MSI2 knockdown/NLK overexpression epistasis, in vivo liver metastasis model Cancer cell international Medium 39097735
2024 MSI2 is a myogenin target gene; Msi2 knockdown in murine myoblasts blocked differentiation and impaired autophagosome formation (reduced LC3) without affecting MyoD or myogenin expression; forced autophagy activation rescued MSI2 loss differentiation defects. Msi2-KO mice had smaller limb muscles and impaired exercise performance. shRNA knockdown, MSI2 overexpression, autophagy rescue, flow cytometry, in vivo Msi2 KO mouse phenotyping Life science alliance Medium 38373797
2024 MSI2 directly binds ATM mRNA and regulates its translation; MSI2 depletion impaired DNA damage response (DDR) signaling (reduced ATM, altered γH2AX and pCHK1 levels) and sensitized NSCLC cells to PARP inhibitors in vitro and in vivo. RNA immunoprecipitation, KP and KPM2 mouse tumor model comparison, Western blot for DDR markers, PARP inhibitor treatment in vitro and in vivo Research square (preprint also published) Medium 37398283 38659828
2024 MSI2 promotes chemotherapy resistance in T-ALL through posttranscriptional regulation of MYC; MSI2 expression is significantly upregulated in persistent leukemic clones at relapse. Single-cell RNA + TCR sequencing of diagnosis-relapse pairs, targeted single-cell DNA sequencing, in vitro and in vivo functional studies with MSI2 manipulation Blood Medium 37801708
2024 HuD protein interacts with Msi2 transcript and positively regulates MSI2 expression; MSI2 in turn represses APAF1 transcript translation, protecting N2a neuroblastoma cells from mitochondrial apoptosis; reduced HuD→reduced MSI2→increased APAF1→apoptosis. RNA immunoprecipitation, siRNA knockdown, Western blot, apoptosis assay in N2a cells PloS one Low 39680531
2025 β-catenin interacts with MSI2 in myeloid cell lines and primary AML samples; MSI2 knockdown reduced Wnt signaling output (TCF/LEF activity) and suppressed LEF-1 expression and nuclear localization; MSI2 binds LEF1 mRNA partly in a β-catenin-dependent fashion, suggesting post-transcriptional control of LEF-1. Co-immunoprecipitation, RIP-seq, CLIP, MSI2 knockdown, TCF/LEF luciferase reporter, human HSPC expansion assay Oncogene Medium 40301545
2025 PRKCQ-AS1 lncRNA binds MSI2 protein; PRKCQ-AS1 or MSI2 knockdown reduces BMX mRNA stability, ERK phosphorylation, and neuroblastoma cell proliferation; small molecule NSC617570 inhibits PRKCQ-AS1–MSI2 protein interaction and reduces BMX expression and tumor progression in mice. RNA immunoprecipitation-seq, BMX mRNA stability assay, AlphaScreen compound screening, shRNA knockdown, in vivo mouse tumor model Advanced science Medium 40103284
2025 MSI2 nuclear localization is mediated by Importin-7 (IPO7) through an MSI2 nuclear localization signal (NLS); IPO7 promotes nuclear translocation of MSI2 and prevents its cytoplasmic ubiquitin-mediated degradation; in the nucleus, IPO7, MSI2, and c-MYC form a ternary complex that enhances c-MYC mRNA stability and MYC-linked glycolytic reprogramming. Co-immunoprecipitation, nuclear/cytoplasmic fractionation, ubiquitination assay, NLS mutagenesis, mass spectrometry, RNA-seq, Seahorse metabolic analysis, xenograft Translational research Medium 42066897
2026 Alternative splicing generates MSI2 isoforms with distinct subcellular localizations: canonical MSI2-328 localizes to the cytoplasm via a 40-aa region (residues 194–234) and promotes translation; alternatively spliced MSI2-324 localizes predominantly to the nucleus via an 18-aa sequence introduced by an alternative 3' splice acceptor in exon 12, and fails to promote translation. The two isoforms associate with distinct protein networks (translation factors vs. chromatin/pre-mRNA processing factors). Tethered reporter assay, truncation and point mutagenesis, subcellular fractionation/localization imaging, co-immunoprecipitation/proteomics bioRxivpreprint Medium 42239307
2021 MSI2 binds miR-301a-3p and facilitates its mitochondrial distribution in endothelial cells; MSI2 itself localizes to mitochondria of multiple cell types; H2O2 decreases MSI2 in mitochondria and reduces mitochondrial miR-301a-3p; MSI2 overexpression increases and inhibition decreases mitochondrial miR-301a-3p. RNA pull-down followed by label-free quantitative proteomics, Western blot, immunofluorescence colocalization, MSI2 overexpression/inhibition Frontiers in molecular biosciences Low 33553241
2015 MSI1 directly targets Msi2 mRNA (as well as Erh) in spermatogonia as demonstrated by RNA binding experiments; nuclear import protein IPO5 facilitates nuclear translocation of MSI1, releasing MSI1 RNA-binding targets; this establishes MSI2 mRNA as a direct target of MSI1-mediated translational regulation during spermatogenesis. Transgenic Msi1 testis-specific overexpression model, RNA binding target identification, co-immunoprecipitation with IPO5 FASEB journal Low 25782991
2015 MSI2 knockout in mice (gene-trap model) causes impaired follicle development: significant decrease in ovarian mass, developmental blocking of antral follicles, pre-antral follicle atresia, reduced MII oocyte yield (60.9% less), and decreased female fertility (33.1% litter size reduction). Gene-trap KO mouse model, histological follicle staging, hormonal stimulation and oocyte collection, litter size analysis Biomolecules Medium 26131972
2023 MSI2 directly binds the 3'UTR of c-Myc mRNA to stabilize it, upregulating c-Myc protein and downstream glucose-6-phosphate dehydrogenase (G6PD) transcription, thereby enhancing the pentose phosphate pathway in neuroblastoma cells. RNA immunoprecipitation, 3'UTR binding assays, G6PD activity measurement, in vitro proliferation/invasion assays Medical oncology Low 37843625
2024 MSI2 directly binds and stabilizes ENO1 mRNA in acute lymphoblastic leukemia cells; stabilized ENO1 protein then binds and increases stability of RPS3 protein; this circNR3C1/MSI2/ENO1/RPS3 axis promotes ALL cell proliferation and inhibits apoptosis. Co-immunoprecipitation, RNA immunoprecipitation, RNA pull-down, protein stability analysis, xenograft Journal of leukocyte biology Low 41069159
2024 MSI2 directly binds miR-30a-3p via its UAG motif and recruits it to AGO2, facilitating miR-30a-3p loading onto AGO2 to suppress CGRRF1 (a KRAS E3 ubiquitin ligase), thereby stabilizing KRAS and activating the KRAS/ERK pathway to promote chemoresistance. RNA immunoprecipitation, Co-IP of MSI2-AGO2, mRNA/miRNA binding assays, CGRRF1 ubiquitination assay, pharmacological inhibition Neoplasia Medium 39522321
2025 FOXF2 transcription factor directly binds the MSI2 promoter (ChIP and luciferase reporter assays) and promotes MSI2 transcription in pancreatic cancer; MSI2 overexpression suppresses NUMB protein translation; FOXF2 knockdown inhibits MSI2 protein translation and enhances NUMB, suppressing PC progression. Luciferase reporter assay, ChIP, FOXF2/MSI2 knockdown and rescue, xenograft mouse model Oncology reports Medium 38847273
2025 A germline non-coding regulatory variant (rs17834140-T) downregulates HSC-selective MSI2 expression and significantly protects against clonal hematopoiesis and myeloid malignancies; stem cell MSI2 levels modify ASXL1-mutant HSC clonal dominance in experimental models, establishing MSI2 as a key post-transcriptional regulator of human HSC fitness. Population genetic analysis, variant effect modeling, MSI2 CLIP-seq target mapping, ASXL1-mutant HSC clonal competition models bioRxiv (preprint)preprint Medium bio_10.1101_2025.03.24.645017
2026 MSI2 enhances stability of LINC00667 lncRNA; LINC00667 facilitates IRF6 mRNA degradation via Staufen1-mediated mRNA decay; IRF6 transcriptionally suppresses tight junction proteins ZO-1, occludin, and claudin-5. Thus, MSI2 knockdown reduces LINC00667, allows IRF6 accumulation, and increases blood-tumor barrier permeability. MSI2 knockdown, lncRNA stability assay, IRF6 ChIP on TJ promoters, Staufen1 knockdown, BTB permeability assay, doxorubicin uptake The Journal of biological chemistry Medium 41581866

Source papers

Stage 0 corpus · 91 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 An RNAi screen identifies Msi2 and Prox1 as having opposite roles in the regulation of hematopoietic stem cell activity. Cell stem cell 125 20621054
2016 Musashi-2 (MSI2) supports TGF-β signaling and inhibits claudins to promote non-small cell lung cancer (NSCLC) metastasis. Proceedings of the National Academy of Sciences of the United States of America 119 27274057
2022 LncRNA LINC00942 promotes chemoresistance in gastric cancer by suppressing MSI2 degradation to enhance c-Myc mRNA stability. Clinical and translational medicine 114 35073459
2015 Transformation of the intestinal epithelium by the MSI2 RNA-binding protein. Nature communications 114 25774828
2018 Long non-coding RNA DANCR promotes malignant phenotypes of bladder cancer cells by modulating the miR-149/MSI2 axis as a ceRNA. Journal of experimental & clinical cancer research : CR 99 30419948
2017 Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells. Nature genetics 88 28436985
1994 Isolation of a CDC25 family gene, MSI2/LTE1, as a multicopy suppressor of ira1. Yeast (Chichester, England) 88 7941731
2013 The SOX2-interactome in brain cancer cells identifies the requirement of MSI2 and USP9X for the growth of brain tumor cells. PloS one 85 23667531
2003 A novel gene, MSI2, encoding a putative RNA-binding protein is recurrently rearranged at disease progression of chronic myeloid leukemia and forms a fusion gene with HOXA9 as a result of the cryptic t(7;17)(p15;q23). Cancer research 78 12649177
2016 The Novel KLF4/MSI2 Signaling Pathway Regulates Growth and Metastasis of Pancreatic Cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 72 27449499
2022 RNA-binding protein complex LIN28/MSI2 enhances cancer stem cell-like properties by modulating Hippo-YAP1 signaling and independently of Let-7. Oncogene 49 35102250
2022 MALDI-TOF Mass Spectrometry Online Identification of Trichophyton indotineae Using the MSI-2 Application. Journal of fungi (Basel, Switzerland) 43 36294668
2021 Identification of Molds with Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry: Performance of the Newly Developed MSI-2 Application in Comparison with the Bruker Filamentous Fungi Database and MSI-1. Journal of clinical microbiology 38 34319807
2020 RNA-binding protein MSI2 isoforms expression and regulation in progression of triple-negative breast cancer. Journal of experimental & clinical cancer research : CR 37 32448269
2021 Glioma glycolipid metabolism: MSI2-SNORD12B-FIP1L1-ZBTB4 feedback loop as a potential treatment target. Clinical and translational medicine 36 34047477
2018 Transcriptome-wide analysis uncovers the targets of the RNA-binding protein MSI2 and effects of MSI2's RNA-binding activity on IL-6 signaling. The Journal of biological chemistry 35 30126842
2023 ADAR1-dependent miR-3144-3p editing simultaneously induces MSI2 expression and suppresses SLC38A4 expression in liver cancer. Experimental & molecular medicine 32 36599932
2017 Msi2 Maintains Quiescent State of Hair Follicle Stem Cells by Directly Repressing the Hh Signaling Pathway. The Journal of investigative dermatology 32 28143780
2022 Adipocytes-Derived Exosomal microRNA-1224 Inhibits M2 Macrophage Polarization in Obesity-Induced Adipose Tissue Inflammation via MSI2-Mediated Wnt/β-Catenin Axis. Molecular nutrition & food research 31 35616318
2019 ETV4 promotes proliferation and invasion of lung adenocarcinoma by transcriptionally upregulating MSI2. Biochemical and biophysical research communications 30 31253395
2016 MSI2 is required for maintaining activated myelodysplastic syndrome stem cells. Nature communications 28 26898884
2008 EVI1 overexpression in t(3;17) positive myeloid malignancies results from juxtaposition of EVI1 to the MSI2 locus at 17q22. Haematologica 28 18815193
2019 Knockdown of HMGA2 regulates the level of autophagy via interactions between MSI2 and Beclin1 to inhibit NF1-associated malignant peripheral nerve sheath tumour growth. Journal of experimental & clinical cancer research : CR 27 31053152
2017 Msi2 plays a carcinogenic role in esophageal squamous cell carcinoma via regulation of the Wnt/β-catenin and Hedgehog signaling pathways. Experimental cell research 27 29054489
2015 RNA binding protein Musashi-1 directly targets Msi2 and Erh during early testis germ cell development and interacts with IPO5 upon translocation to the nucleus. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 25782991
2021 Musashi-2 (MSI2) regulates epidermal growth factor receptor (EGFR) expression and response to EGFR inhibitors in EGFR-mutated non-small cell lung cancer (NSCLC). Oncogenesis 25 33723247
2020 LncRNA DANCR regulates osteosarcoma migration and invasion by targeting miR-149/MSI2 axis. European review for medical and pharmacological sciences 24 32633342
2015 Up-regulated MSI2 is associated with more aggressive chronic myeloid leukemia. Leukemia & lymphoma 23 25363400
2020 The Musashi proteins MSI1 and MSI2 are required for photoreceptor morphogenesis and vision in mice. The Journal of biological chemistry 22 33168629
2021 Myofibroblast-Specific Msi2 Knockout Inhibits HCC Progression in a Mouse Model. Hepatology (Baltimore, Md.) 21 33609283
2020 MicroRNA-149 suppresses the malignant phenotypes of ovarian cancer via downregulation of MSI2 and inhibition of PI3K/AKT pathway. European review for medical and pharmacological sciences 21 31957818
2020 Knockdown of MIR4435-2HG Suppresses the Proliferation, Migration and Invasion of Cervical Cancer Cells via Regulating the miR-128-3p/MSI2 Axis in vitro. Cancer management and research 21 33061572
2017 Differential DNA methylation of MSI2 and its correlation with diabetic traits. PloS one 21 28542303
2021 Dual Knockdown of Musashi RNA-Binding Proteins MSI-1 and MSI-2 Attenuates Putative Cancer Stem Cell Characteristics and Therapy Resistance in Ovarian Cancer Cells. International journal of molecular sciences 20 34768932
2021 Msi2-mediated MiR7a-1 processing repression promotes myogenesis. Journal of cachexia, sarcopenia and muscle 20 34877814
2019 Emerging roles of the long non-coding RNA 01296/microRNA-143-3p/MSI2 axis in development of thyroid cancer. Bioscience reports 20 31693087
2017 RNA binding protein MSI2 positively regulates FLT3 expression in myeloid leukemia. Leukemia research 20 28107692
2015 Knockout of RNA Binding Protein MSI2 Impairs Follicle Development in the Mouse Ovary: Characterization of MSI1 and MSI2 during Folliculogenesis. Biomolecules 20 26131972
2013 MSI2 expression is decreased in grade II of gastric carcinoma. Pathology, research and practice 20 24002004
2024 Clonal evolution dissection reveals that a high MSI2 level promotes chemoresistance in T-cell acute lymphoblastic leukemia. Blood 19 37801708
2011 Roles for MSI2 and PROX1 in hematopoietic stem cell activity. Current opinion in hematology 19 21577104
2019 MSI2-TGF-β/TGF-β R1/SMAD3 positive feedback regulation in glioblastoma. Cancer chemotherapy and pharmacology 17 31250154
2022 KLF4 suppresses the proliferation and metastasis of NSCLC cells via inhibition of MSI2 and regulation of the JAK/STAT3 signaling pathway. Translational oncology 15 35580385
2021 Identification of gene targets of mutant C/EBPα reveals a critical role for MSI2 in CEBPA-mutated AML. Leukemia 15 33623142
2021 Downregulation of SOX2-OT Prevents Hepatocellular Carcinoma Progression Through miR-143-3p/MSI2. Frontiers in oncology 14 34322386
2020 Integrated genetic and epigenetic analyses uncover MSI2 association with allergic inflammation. The Journal of allergy and clinical immunology 14 32795589
2022 Integrative genome-wide analysis reveals EIF3A as a key downstream regulator of translational repressor protein Musashi 2 (MSI2). NAR cancer 13 35528200
2019 Upregulation of microRNA-143-3p induces apoptosis and suppresses proliferation, invasion, and migration of papillary thyroid carcinoma cells by targeting MSI2. Experimental and molecular pathology 13 31738908
2023 MSI2 promotes translation of multiple IRES-containing oncogenes and virus to induce self-renewal of tumor initiating stem-like cells. Cell death discovery 12 37117191
2017 Anticancer effect of quinacrine on diffuse large B‑cell lymphoma via inhibition of MSI2‑NUMB signaling pathway. Molecular medicine reports 11 29115587
2012 Drosophila Rbp6 is an orthologue of vertebrate Msi-1 and Msi-2, but does not function redundantly with dMsi to regulate germline stem cell behaviour. PloS one 11 23209605
2021 LncRNA TUG1 promotes Ewing's sarcoma cell proliferation, migration, and invasion via the miR-199a-3p-MSI2 signaling pathway. Neoplasma 10 33780263
2025 The Super Enhancer-Driven Long Noncoding RNA PRKCQ-AS1 Promotes Neuroblastoma Tumorigenesis by Interacting With MSI2 Protein and Is Targetable by Small Molecule Compounds. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 9 40103284
2023 MSI2 deficiency in ILC3s attenuates DSS-induced colitis by affecting the intestinal microbiota. Frontiers in immunology 9 36713428
2021 RNA-Binding Protein MSI2 Binds to miR-301a-3p and Facilitates Its Distribution in Mitochondria of Endothelial Cells. Frontiers in molecular biosciences 9 33553241
2024 MSI2 regulates NLK-mediated EMT and PI3K/AKT/mTOR pathway to promote pancreatic cancer progression. Cancer cell international 8 39097735
2020 Knockdown of MSI2 inhibits metastasis by interacting with caveolin-1 and inhibiting its ubiquitylation in human NF1-MPNST cells. Cell death & disease 8 32606289
2014 Blast crisis Ph+ chronic myeloid leukemia with NUP98/HOXA13 up-regulating MSI2. Molecular cytogenetics 8 24971156
2023 MSI2 Modulates Unsaturated Fatty Acid Metabolism by Binding FASN in Bovine Mammary Epithelial Cells. Journal of agricultural and food chemistry 7 38059915
2018 MSI2 knockdown represses extrahepatic cholangiocarcinoma growth and invasion by inhibiting epithelial-mesenchymal transition. OncoTargets and therapy 7 30034243
2023 Msi2 enhances muscle dysfunction in a myotonic dystrophy type 1 mouse model. Biomedical journal 6 37797921
2025 β-Catenin interacts with canonical RBPs including MSI2 to associate with a Wnt signalling mRNA network in myeloid leukaemia cells. Oncogene 5 40301545
2025 Prolonged DEHP exposure enhances the stemness and metastatic potential of TNBC cells in an MSI2-dependent manner. International journal of biological sciences 4 39990676
2024 The RNA-binding protein Msi2 regulates autophagy during myogenic differentiation. Life science alliance 4 38373797
2023 Musashi-2 (MSI2) promotes neuroblastoma tumorigenesis through targeting MYC-mediated glucose-6-phosphate dehydrogenase (G6PD) transcriptional activation. Medical oncology (Northwood, London, England) 4 37843625
2016 The Human MSI2 Gene is Associated with Schizophrenia in the Chinese Han Population. Neuroscience bulletin 4 27059221
2024 Transcription factor FOXF2 promotes the development and progression of pancreatic cancer by targeting MSI2. Oncology reports 3 38847273
2023 Detection of a Novel MSI2-C17orf64 Transcript in a Patient with Aggressive Adenocarcinoma of the Gastroesophageal Junction: A Case Report. Genes 3 37107676
2022 Competitive evolved sub-clonal BCR::ABL1 and novel MSI2::PC fusion genes in myelodysplastic syndrome with isolated del(5q). Hematological oncology 3 36301018
2025 ELK4 transcription promotes MSI2-mediated progression of non-small cell lung cancer through the TGF-β/SMAD3 pathway. The Kaohsiung journal of medical sciences 2 39969091
2025 Blocking MSI2 alleviated radiation-induced pulmonary fibrosis through inhibiting epithelial-mesenchymal transition. International journal of radiation biology 2 40227576
2025 Specific MSI2 deletion maintains intestinal barrier integrity by down-regulating ILC3s-derived IL-17 a in mice with colitis. International immunopharmacology 2 40279942
2025 miR-107 represses DMPK and is sequestered by CUG repeats triggering the MSI2/miR-7 pathogenesis axis in myotonic dystrophy. Molecular therapy. Nucleic acids 2 40599975
2025 A Circular RNA Promotes Tumor Metastasis through Stabilizing MSI2 Protein in Pancreatic Ductal Adenocarcinoma. Research (Washington, D.C.) 2 41049614
2024 A novel regulatory axis of MSI2-AGO2/miR-30a-3p-CGRRF1 drives cancer chemoresistance by upregulating the KRAS/ERK pathway. Neoplasia (New York, N.Y.) 2 39522321
2024 HuD regulates apoptosis in N2a cells by regulating Msi2 expression. PloS one 2 39680531
2023 Musashi-2 (MSI2) regulation of DNA damage response in lung cancer. bioRxiv : the preprint server for biology 2 37398283
2025 LncRNA FGD5-AS1 Facilitates Hepatocellular Carcinoma Cell Stemness by Enhancing PKD1 mRNA Stability Through Binding With MSI2. Molecular carcinogenesis 1 39803743
2024 Musashi-2 (MSI2) regulation of DNA damage response in lung cancer. Research square 1 38659828
2020 Unravelling the drugability of MSI2 RNA recognition motif (RRM) protein and the prediction of their effective antileukemia inhibitors from traditional herb concoctions. Journal of biomolecular structure & dynamics 1 33131412
2026 MSI2 expression in single vs. double dominant follicles and its role in Mongolian sheep fecundity. Animal reproduction science 0 41564630
2026 The RNA-binding protein MSI2 controls blood-tumor barrier permeability via LINC00667-Mediated IRF6 mRNA decay. The Journal of biological chemistry 0 41581866
2026 MATR3 regulates METTL3-Mediated m6A modification of MSI2 mRNA to activate the Wnt/β-Catenin pathway, exacerbating myocardial fibrosis and atrial fibrillation. Journal of bioenergetics and biomembranes 0 41849072
2026 Importin-7 facilitates cervical cancer progression through MSI2 nuclear import and is associated with MSI2-MYC-linked glycolytic reprogramming. Translational research : the journal of laboratory and clinical medicine 0 42066897
2026 Multi‑omics identification of MSI2 as a super-enhancer‑driven vulnerability in MYCN‑amplified neuroblastoma. Journal of translational medicine 0 42143291
2026 Isoform-Specific Localization Diversifies Human MSI2 Function. bioRxiv : the preprint server for biology 0 42239307
2025 CircNR3C1 promotes acute lymphoblastic leukemia progression via the MSI2/ENO1/RPS3 axis. Journal of leukocyte biology 0 41069159
2025 MSI2 exerts antitumor effects by regulating T-cell function in kidney renal clear cell carcinoma. Translational andrology and urology 0 41368259
2025 MSI2 in the dentate gyrus and ovary regulates the reproductive endocrine homeostasis of female mice. Communications biology 0 41437114
2021 [Corrigendum] Anticancer effect of quinacrine on diffuse large B‑cell lymphoma via inhibition of MSI2‑NUMB signaling pathway. Molecular medicine reports 0 33398369
2015 [Influence of RNA interference on MSI-2 gene in THP-1 cell and expression of NUMB]. Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi 0 26477766

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