Ask about this productRelated genes to: MBNL2 antibody
- Gene:
- MBNL2 NIH gene
- Name:
- muscleblind like splicing regulator 2
- Previous symbol:
- -
- Synonyms:
- MBLL, MBLL39
- Chromosome:
- 13q32.1
- Locus Type:
- gene with protein product
- Date approved:
- 2003-03-05
- Date modifiied:
- 2016-10-05
Related products to: MBNL2 antibody
Related articles to: MBNL2 antibody
- Chemotherapy drug-induced changes of gene expression in the dorsal root ganglion (DRG) are critical for the genesis of chemotherapy-induced neuropathic pain (CINP). However, the mechanisms driving these changes remain elusive. Here, we report the downregulation of muscleblind-like protein 2 (MBNL2), an RNA-binding protein, in the DRG neurons after intraperitoneal injection of paclitaxel. Rescuing this downregulation blocks an increase of the C-C chemokine receptor type 2 (CCR2) in the DRG and mitigates paclitaxel-induced mechanical allodynia, heat and cold hyperalgesia and ongoing pain. Conversely, DRG downregulation of MBNL2 increases the expression of CCR2 in the DRG neurons and leads to CINP-like symptoms in naïve mice. Mechanistically, paclitaxel-induced downregulation of MBNL2 reduces its binding to the 3'-untranslated region of Ccr2 mRNA, thereby enhancing the stability of Ccr2 mRNA in the DRG. Given that MBNL2 and CCR2 are co-expressed in DRG neurons, these findings suggest that MBNL2 alleviates CINP, likely by destabilizing CCR2 expression in the DRG, and may represent a promising therapeutic strategy for this condition. - Source: PubMed
Publication date: 2026/04/11
Yan KeshiMa RuiningWang BingFeng XiaozhouLi XinjuMeng XiangleiShang HuijieKidd Benjamin MSwanson Maurice SHu HuijuanTao Yuan-Xiang - Opioid and methamphetamine use disorders (OUD and MUD) are characterized by enduring neural adaptations within brain reward circuitry, yet the cell-type-specific post-transcriptional mechanisms underlying these changes remain poorly understood. While microglia are essential for maintaining central nervous system homeostasis and modulating neuroinflammatory responses to drugs of abuse, their alternative splicing (AS) programs have not been defined in the context of addiction. This study characterized the microglial AS landscape in the mouse dorsal striatum during morphine and methamphetamine intravenous self-administration (IVSA), as well as following a 21-day period of abstinence. Analysis of RNA-sequencing data using rMATS and DEXSeq revealed that both drugs significantly dysregulate core splicing machinery, with skipped exons (SE) emerging as the most prevalent splicing event. Notably, morphine exposure induced a robust persistent splicing signature, comprising 736 exonic regions in 221 genes that remained altered through abstinence, whereas methamphetamine-induced changes were primarily reversible. Functional annotation predicted that approximately 27.5% of these events induce frameshifts, potentially impacting critical microglial pathways such as autophagy ( ), chromatin remodeling ( ), and RNA processing ( ). These findings identify previously unrecognized post-transcriptional neuroimmune mechanisms and suggest that persistent splicing dysregulation in microglia may contribute to the long-term pathophysiology of OUD. - Source: PubMed
Publication date: 2026/04/05
Margetts Alexander VBystrom Lauren LVilca Samara JTuesta Luis M - Muscleblind-like (MBNL) RNA-binding proteins (RBPs) possess modular domains that mediate regulation of alternative splicing and RNA localization. Myotonic Dystrophy Type 1 is a CTG repeat expansion disorder where MBNL is sequestered into intranuclear RNA foci, impairing its function. Previous studies found that MBNL self-associates through its exon 7, but the nature of this interaction is not well understood. We identified a cysteine in MBNL1 exon 7 that enables dimerization through formation of an intermolecular disulfide bond. We likewise demonstrate that MBNL2 dimerizes by forming disulfide bonds between multiple cysteines in its carboxy-terminus. Nucleocytoplasmic fractionation revealed a greater proportion of MBNL1 dimer in the nucleus, suggesting a nuclear function for the MBNL1 dimer. We investigated a connection between MBNL1 dimerization and MBNL1-mediated regulation of alternative splicing. To accomplish this, we mutated the MBNL1 cysteine in question to alanine (C325A) and performed RNAseq. We uncovered novel splicing events sensitive to MBNL1 dimerization. We also found that MBNL1 C325A, when co-expressed with expanded CTG repeats, produces smaller, more numerous foci, suggesting a role for the MBNL1 dimer in maintaining foci integrity. These results provide insight into biological and pathological mechanisms of MBNL1 dimerization and suggest other RBPs might similarly dimerize to regulate function. - Source: PubMed
Publication date: 2026/03/26
Knudson Luke AKosti AdamMoss Kathryn RShi LiangNguyen GiaLinh NJanusz-Kaminska AleksandraZhou Eric XHildebrandt Ryan PWang Eric TBassell Gary J - Myotonic dystrophy type 1 (DM1) arises from toxic CUG-expanded DMPK transcripts that sequester Muscleblind-like (MBNL) proteins, yet how this molecular lesion perturbs brain development in congenital DM1 (CDM) remains unknown. Here, we identify an unanticipated developmental role for MBNL2 in outer radial glial cells, a progenitor population critical for cortical expansion. We demonstrate that MBNL2 is expressed in these cells both in vivo and in forebrain organoids derived from patient-specific human induced pluripotent stem cells (hiPSCs), rendering them particularly sensitive to MBNL2 titration. Using genome editing to excise the CTG repeats in the DMPK gene, we provide evidence that the expanded trinucleotide tract directly contributes to defective neuronal migration and impaired differentiation of late-born cortical neurons in CDM organoids. These findings redefine MBNL2 as a potential regulator of human corticogenesis and uncover a developmental mechanism by which RNA toxicity drives this severe form of DM1. By revealing a prenatal origin for CDM neuropathology linked to MBNL2 dysfunction, this work opens avenues for therapeutic strategies targeting early developmental windows. - Source: PubMed
Publication date: 2026/02/03
De Serres-Bérard ThiéryGosztyla Maya LNguyen GradyYeo Gene WPuymirat JackChahine Mohamed - Myotonic dystrophy type 1 (DM1) is the most common adult-onset muscular dystrophy and severely affects multiple organ systems, including the brain, heart, skeletal muscle, and gastrointestinal (GI) tract. Despite 80% of individuals with DM1 experiencing GI dysfunction that affects their daily life, the mechanisms of GI dysmotility in DM1 remain an understudied aspect of the disease. DM1 is caused by a CTG repeat expansion in the gene that, when expressed as an expanded CUG repeat RNA, sequesters and reduces the activity of the muscleblind-like (MBNL) RNA-binding protein family. We developed a mouse line with conditional, smooth muscle-specific knockout of and to model and investigate myogenic mechanisms contributing to GI dysmotility in DM1. Mice with knockout exhibited delayed GI transit of small and large bowel in vivo and increased smooth muscle contractile tone of jejunum and colon segments ex vivo. Smooth muscle from the jejunum and colon showed no histopathology suggesting an intrinsic defect and contained increased phosphorylation of the 20 kDa myosin light chain (Mlc20), consistent with increased contraction. RNA sequencing of mouse and human DM1 GI samples enriched for smooth muscle revealed conserved misregulated alternative splicing of transcripts associated with the regulation of Mlc20 phosphorylation and smooth muscle contraction. These findings demonstrate that knockout disrupts the regulation of contraction dynamics and causes GI smooth muscle hyperactivity, suggesting that therapeutics that reduce GI contractile activity may improve DM1 GI symptoms. - Source: PubMed
Publication date: 2025/12/11
Peterson Janel A MFrias Jesus AMiller Andrew NSoni Krishnakant GZhang YiXia ZhengDay John WPreidis Geoffrey ACooper Thomas A