Function
Mediates pre-mRNA alternative splicing regulation. Acts either as activator or repressor of splicing on specific pre-mRNA targets. Inhibits cardiac troponin-T (TNNT2) pre-mRNA exon inclusion but induces insulin receptor (IR) pre-mRNA exon inclusion in muscle. Antagonizes the alternative splicing activity pattern of CELF proteins. Regulates the TNNT2 exon 5 skipping through competition with U2AF2. Inhibits the formation of the spliceosome A complex on intron 4 of TNNT2 pre-mRNA. Binds to the stem-loop structure within the polypyrimidine tract of TNNT2 intron 4 during spliceosome assembly. Binds to the 5'-YGCU(U/G)Y-3'consensus sequence. Binds to the IR RNA. Binds to expanded CUG repeat RNA, which folds into a hairpin structure containing GC base pairs and bulged, unpaired U residues.
Gene References into Functions
- RBFOX1/MBNL1 competition for CCUG RNA repeats binding contributes to myotonic dystrophy type 1/type 2 differences. PMID: 29789616
- Functional depletion of the alternative splicing factors Muscleblind-like (MBNL 1 and 2) is at the basis of the neuromuscular disease myotonic dystrophy type 1 (DM1). Here, we screen for miRNAs that regulate MBNL1 and MBNL2 in HeLa cells. We thus identify miR-23b and miR-218, and confirm that they downregulate MBNL proteins in this cell line. PMID: 29946070
- For exogenous activation of MBNL transcription, MBNL1 transcription start site T2 seems to be the most suitable target, as the ensuing pre-mRNA is susceptible to both major loops, e1 and e5, and hence, theoretically, following induction each cell in the body could reach the optimal MBNL content. PMID: 28949831
- RAN Translation Regulated by Muscleblind Proteins in Myotonic Dystrophy Type 2 PMID: 28910618
- Our work suggests that DM1 patients are at risk for Fuchs' endothelial corneal dystrophy (FECD). DMPK mutations contribute to the genetic burden of FECD but are uncommon. We establish a connection between two repeat expansion disorders converging upon RNA-MBNL1 foci and FECD. PMID: 28886202
- Binding of the MBNL zinc fingers to cardiac troponin T pre-mRNA is specific and relatively simple, unlike the complex multiple dimer-trimer stoichiometries postulated in some previous studies. PMID: 28718627
- Heterozygous missense mutations and one in-frame deletion in MBNL1 were identified in 3 myotonic dystrophy patients. PMID: 27222292
- Nuclear retention of full-length HTT RNA is mediated by splicing factors MBNL1 and U2AF65 PMID: 26218986
- muscleblind-like 1 (MBNL1) is a robust suppressor of multiorgan breast cancer metastasis. It binds the 3' untranslated regions of DBNL and TACC1 -two genes that are implicated as metastasis suppressors. PMID: 26883358
- Sense DMPK RNA foci clearly co-localize with MBNL1 and MBNL2 proteins and accumulate in myotonic dystrophy 1 tissues during development. PMID: 26339785
- abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform. PMID: 26018658
- Reduced RBFOX1 activity in myotonic dystrophy type 1 tissues may amplify several of the splicing alterations caused by the deficiency in MBNL1. PMID: 25211016
- MBNL1 binds with C allelic pre-miR-1307 leading to low expression of miR-1307-3p in colorectal cancer. PMID: 25977444
- The result is consistent with the hypothesis that MBNL proteins are trapped by expanded CUG repeats and inactivated in myotonic dystrophy type 1 (DM1) and that CELF1 is activated in DM1. PMID: 25403273
- Results show that nuclear localization is a major determinant of MBNL1 function. It promotes the nuclear retention of repeat-containing transcripts, which results in repression of aberrant protein expression from the expanded repeats. PMID: 25274774
- Results highlight the importance of RNA binding by MBNL Zinc Finger domains 1 and 2 for splicing regulatory activity, even when the protein is artificially recruited to its regulatory location on target RNAs. PMID: 24373687
- both MBNL1 and MBNL2 are involved in the regulation of Tau exon 2 splicing and the mis-splicing of Tau in DM1 is due to the combined inactivation of both. PMID: 24440524
- MBNL1 and RBFOX2 cooperate to establish a splicing programme involved in pluripotent stem cell differentiation. PMID: 24048253
- MBNL1 is highly mobile and changes localization in response to altered transcription and splicing activity, providing an insight into the sensitivity of the lens to changes in MBNL1 distribution. PMID: 24354850
- in both dystrophic and sarcopenic muscles MBNL1 undergoes intranuclear relocation, accumulating in its usual functional sites but also ectopically moving to domains which are usually devoid of this protein in healthy adults PMID: 23807294
- This report demonistrated that the association of several genetic variants of the MBNL1 gene with DM1 or with the severity of the disease. PMID: 23161457
- consistent with a central and negative regulatory role for MBNL proteins in pluripotency, their knockdown significantly enhances the expression of key pluripotency genes and the formation of induced pluripotent stem cells during somatic cell reprogramming PMID: 23739326
- MBNL1 loss shows a graded effect on the number and severity of the ensuing RNA splice defects. PMID: 23166594
- study suggests that regulation of CUGBP1 and MBNL1 is essential for accurate control of destabilization of a broad spectrum of mRNAs as well as of alternative splicing events PMID: 22355723
- It was demonstrated that functionally distinct classes of MBNL1-mediated splicing events exist as defined by requirements for zinc finger-RNA interactions. PMID: 22890842
- The present results show that the MBNL1 protein is expressed and more or less sequestered into the CCUGexp nuclear foci also in analyzed non-muscle tissues of DM2 patients. PMID: 22520280
- congenital myotonic dystrophy muscle has nuclear foci that contain muscleblind-like 1 (MBNL1) protein. PMID: 22113158
- The removal of one pair of zinc fingers greatly impairs the binding affinity of MBNL1, which indicates that the two pairs of zinc fingers might possibly interact with RNA targets cooperatively. PMID: 22106026
- Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis. PMID: 22306654
- Expanded CUG repeats Dysregulate RNA splicing by altering the stoichiometry of the muscleblind 1 complex PMID: 21900255
- Deletion of the MBNL1 response element eliminated MBNL1 splicing regulation and led to complete inclusion of exon 5, which is consistent with the suppressive effect of MBNL1 on splicing. PMID: 21832083
- Although MBNL1 contains four Zn fingers, it appears that only two Zn fingers binding GC motifs are necessary for high affinity RNA binding. PMID: 21548961
- MBNL1 regulates pre-miR-1 biogenesis. PMID: 21685920
- results indicate the occurrence of a mis-splicing event in myotonic dystrophy type 1 that is induced neither by a loss of muscleblind-like 1 (MBNL1) function nor by a gain of CUGBP1 PMID: 21439371
- the abnormally high inclusion of the exon 5 and 7 regions in DM1 is expected to enhance the potential of MBNL1 of being sequestered with nuclear CUG expansions, which provides new insight into DM1 pathophysiology. PMID: 21454535
- Findings demonstrate a role for Mbnl1 in controlling insulin receptor exon 11 inclusion via binding to a downstream intronic enhancer element. PMID: 20519504
- MBNL proteins promote opposite splicing patterns for cardiac troponin T and insulin receptor alternative exons PMID: 15257297
- small interfering RNA-mediated down-regulation of MBNL1 in normal myoblasts results in abnormal insulin receptor splicing PMID: 15546872
- The GFP-MBNL1 in CUG and CAG foci have similar half-times of recovery and fractions of immobile molecules, suggesting GFP-MBNL1 is bound by both CUG and CAG repeats and formation of RNA foci and disruption of MBNL1-regulated splicing are separable events. PMID: 15961406
- The fact that a human protein works in a Drosophila cellular context illustrates the use of an in vivo test to prove functional conservation. PMID: 16394256
- findings show that MBNL1 nuclear sequestration in protein foci is a molecular pathology marker of DM1 and DM2 patients where ribonuclear inclusions of transcripts with expanded CUG/CCUG repeats are also present PMID: 16920640
- Elevated levels of MBNL1 show RNA-independent interaction with hnRNP H and dampen the inhibitory activity of increased hnRNP H levels on IR splicing in normal myoblasts. PMID: 16946708
- MBNL1 (muscleblind-like protein 1) is an alternative splicing factor that becomes highly concentrated with mutant RNA foci. PMID: 17846170
- MBNL may bind all of its RNA substrates, both normal and pathogenic, as structured stem-loops containing pyrimidine mismatches. PMID: 17942744
- Examination of dynamics of MBNL1 in response to stress, and suggestion of a role for MBNL1 in mRNA metabolism in the cytoplasm. PMID: 18335541
- Both the ZnF3 and the ZnF4 zinc-finger domains target GC steps, with site-specific recognition mediated by a network of hydrogen bonds formed primarily with main chain groups of the protein. PMID: 19043415
- MBNL1 and MBNL2 always co-distributed. Functional differences between MBNL1 and MBNL2 have not yet been found PMID: 19095965
- Our data seem indicate that the presence of ribonuclear inclusions and MBNL1 nuclear foci are involved in alteration of alternative splicing but do not impair DM2 myogenic differentiation. PMID: 19345584
- Data show that ligand 1 selectively destabilizes the MBNL1N-poly(CUG) complex. PMID: 19805260
Show More
Hide All
Involvement in disease
Dystrophia myotonica 1 (DM1); Corneal dystrophy, Fuchs endothelial, 3 (FECD3)
Subcellular Location
Nucleus. Cytoplasm. Cytoplasmic granule. Note=Localized with DDX1, TIAL1 and YBX1 in stress granules upon stress (PubMed:18335541). Localized in the cytoplasm of multinucleated myotubes (PubMed:18335541). Colocalizes with nuclear foci of retained expanded-repeat transcripts in myotubes from patients affected by myotonic dystrophy (PubMed:10970838, PubMed:11590133, PubMed:11929853).
Protein Families
Muscleblind family
Tissue Specificity
Highly expressed in cardiac, skeletal muscle and during myoblast differentiation. Weakly expressed in other tissues (at protein level). Expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.
