Myotonic dystrophy type 1 (DM1) is caused by a CUGn expansion (n approximately 50 to 5000) in the 3' untranslated region of the mRNA of the DM protein kinase gene. We show that mutant RNA binds and sequesters transcription factors (TFs), with up to 90% depletion of selected TFs from active chromatin. Diverse genes are consequently reduced in expression, including the ion transporter CIC-1, which has been implicated in myotonia. When TF specificity protein 1 (Sp1) was overexpressed in DM1-affected cells, low levels of messenger RNA for CIC-1 were restored to normal. Transcription factor leaching from chromatin by mutant RNA provides a potentially unifying pathomechanistic explanation for this disease.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1126/science.1088679 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Altered mitochondrial unfolded protein response and FGF21 secretion in MASLD progression and the effect of exercise intervention.
Sci Rep
January 2025
School of Sports and Health, Nanjing Sport Institute, Nanjing, China.
A high-calorie diet and lack of exercise are the most important risk factors contributing to metabolic dysfunction-associated steatotic liver disease (MASLD) initiation and progression. The precise molecular mechanisms of mitochondrial function alteration during MASLD development remain to be fully elucidated. In this study, a total of 60 male C57BL/6J mice were maintained on a normal or amylin liver NASH (AMLN) diet for 6 or 10 weeks.
View Article and Find Full Text PDFSP-1-activated LINC01016 overexpression promotes gastric cancer invasion and metastasis through inhibiting EIF4A3-mediated MMP9 mRNA decay.
Cell Death Dis
January 2025
Department of Pathology, Qilu Hospital and School of Basic Medical Sciences Shandong University, Jinan, Shandong, PR China.
Long noncoding RNAs (lncRNAs) are key regulators during gastric cancer (GC) development and may be viable treatment targets. In the present study, we showed that the expression of the long intergenic noncoding RNA 01016 (LINC01016) is significantly higher in GC tissues with lymph node metastasis (LNM) than those without LNM. LINC01016 overexpression predicts a poorer relapse-free survival (RFS) and overall survival (OS).
View Article and Find Full Text PDFRole of PGC-1α in the proliferation and metastasis of malignant tumors.
J Mol Histol
January 2025
Department of Thoracic Surgery, Lung Cancer Diagnosis and Treatment Center of Dalian, The First Affiliated Hospital of Dalian Medical University, Dalian, 116011, China.
Malignant tumors are among the major diseases threatening human survival in the world, and advancements in medical technology have led to a steady increase in their detection rates worldwide. Despite unique clinical presentations across the spectrum of malignancies, treatment modalities generally adhere to common strategies, encompassing primarily surgical intervention, radiation therapy, chemotherapy, and targeted treatments. Uncovering the genetic elements contributing to cancer cell proliferation, metastasis, and drug resistance remains a pivotal pursuit in the development of novel targeted therapeutics.
View Article and Find Full Text PDFHalofuginone prevents inflammation and proliferation of high-altitude pulmonary hypertension by inhibiting the TGF-β1/Smad signaling pathway.
Sci Rep
January 2025
General Hospital of Xinjiang Military Command, 359 North Friendship Road, Sayibak, Ürümqi, 830000, Xinjiang, China.
The inflammatory response of lung tissue and abnormal proliferation of pulmonary artery smooth muscle cells are involved in the pathogenesis of high-altitude pulmonary hypertension (HAPH). Halofuginone (HF), an active ingredient derivative of Chang Shan (Dichroa febrifuga Lour. [Hydrangeaceae]), has antiproliferative, antihypertrophic, antifibrotic, and other effects, but its protective effects on HAPH remains unclear.
View Article and Find Full Text PDFMolecular and pharmacological heterogeneity of ETV6::RUNX1 acute lymphoblastic leukemia.
Nat Commun
January 2025
Department of Pharmacy and Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
ETV6::RUNX1 is the most common fusion gene in childhood acute lymphoblastic leukemia (ALL) associated with favorable prognosis, but the optimal therapy for this subtype remains unclear. Profiling the genomic and pharmacological landscape of 194 pediatric ETV6::RUNX1 ALL cases, we uncover two transcriptomic clusters, C1 (61%) and C2 (39%). Compared to C1, the C2 subtype features higher white blood cell counts and younger age at diagnosis, as well as better early treatment responses.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!