ArticleNucleic acids research2014
Muscleblind-like 1 activates insulin receptor exon 11 inclusion by enhancing U2AF65 binding and splicing of the upstream intron.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Commitment to Myogenic Differentiation Significantly Aggravates the RNA Phenotype in Myotonic Dystrophy Type 1.Neuropathology and applied neurobiology · 2026Article
- Myotonic dystrophy type 1: clinical diversity, molecular insights and therapeutic perspectives.Nature reviews. Neurology · 2025Review
- The Role of NRF2 in Trinucleotide Repeat Expansion Disorders.Antioxidants (Basel, Switzerland) · 2024Review
- A 3'-pre-tRNA-derived small RNA tRF-1-Ser regulated by 25(OH)D promotes proliferation and stemness by inhibiting the function of MBNL1 in breast cancer.Clinical and translational medicine · 2024Article
- U2AF2-SNORA68 promotes triple-negative breast cancer stemness through the translocation of RPL23 from nucleoplasm to nucleolus and c-Myc expression.Breast cancer research : BCR · 2024Article
- Modulatory role of RNA helicases in MBNL-dependent alternative splicing regulation.Cellular and molecular life sciences : CMLS · 2023Article
- Dynamics and variability of transcriptomic dysregulation in congenital myotonic dystrophy during pediatric development.Human molecular genetics · 2023Article
- CHERP Regulates the Alternative Splicing of pre-mRNAs in the Nucleus.International journal of molecular sciences · 2022Article
- Gamma-glutamyl-leucine levels are causally associated with elevated cardio-metabolic risks.Frontiers in nutrition · 2022Article
- Review
- Oxidative Stress in DNA Repeat Expansion Disorders: A Focus on NRF2 Signaling Involvement.Biomolecules · 2020Review
- Microenvironmental Determinants of Breast Cancer Metastasis: Focus on the Crucial Interplay Between Estrogen and Insulin/Insulin-Like Growth Factor Signaling.Frontiers in cell and developmental biology · 2020Review
- RNA processing in skeletal muscle biology and disease.Transcription · 2019Review
- OTUB2 stabilizes U2AF2 to promote the Warburg effect and tumorigenesis via the AKT/mTOR signaling pathway in non-small cell lung cancer.Theranostics · 2019Article
- MBNL1 alternative splicing isoforms play opposing roles in cancer.Life science alliance · 2018Article
- MBNL splicing activity depends on RNA binding site structural context.Nucleic acids research · 2018Article
- Alternative splicing analysis in human monocytes and macrophages reveals MBNL1 as major regulator.Nucleic acids research · 2018Article
- Molecular basis of titin exon exclusion by RBM20 and the novel titin splice regulator PTB4.Nucleic acids research · 2018Article
- How alternative splicing affects membrane-trafficking dynamics.Journal of cell science · 2018Review
- In vitro iCLIP-based modeling uncovers how the splicing factor U2AF2 relies on regulation by cofactors.Genome research · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Alternative splicing regulates developmentally and tissue-specific gene expression programs, disruption of which have been implicated in numerous diseases. Muscleblind-like 1 (MBNL1) regulates splicing transitions, which are disrupted on loss of MBNL1 function in myotonic dystrophy type 1 (DM1). One such event is MBNL1-mediated activation of insulin receptor exon 11 inclusion, which requires an intronic enhancer element downstream of exon 11. The mechanism of MBNL1-mediated activation of exon inclusion is unknown. We developed an in vitro splicing assay, which robustly recapitulates MBNL1-mediated splicing activation of insulin receptor exon 11 and found that MBNL1 activates removal of the intron upstream of exon 11 upon binding its functional response element in the downstream intron. MBNL1 enhances early spliceosome assembly as evidenced by enhanced complex A formation and binding of U2 small nuclear ribonucleoprotein auxiliary factor 65 kDa subunit (U2AF65) on the upstream intron. We demonstrated that neither the 5' splice site nor exon 11 sequences are required for MBNL1-activated U2AF65 binding. Interestingly, the 5' splice site is required for MBNL1-mediated activation of upstream intron removal, although MBNL1 has no effect on U1 snRNA recruitment. These results suggest that MBNL1 directly activates binding of U2AF65 to enhance upstream intron removal to ultimately activate alternative exon inclusion.
Indexed as
Identifiers
What OpenQuestion holds
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.