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TCF3, also known as E2A, is a well-studied transcription factor that plays an important role in stem cell maintenance and hematopoietic development. The gene encodes two related proteins, E12 and E47, which arise from mutually exclusive alternative splicing (MEAS). Since these two proteins have different DNA binding and dimerization domains, this AS event must be strictly regulated to ensure proper isoform ratios. Previously, we found that heterogeneous nuclear ribonucleoprotein (hnRNP) H1/F regulates TCF3 AS by binding to exonic splicing silencers (ESSs) in exon 18b. Here, we identify conserved intronic splicing silencers (ISSs) located between, and far from, the two mutually exclusive exons, and show that they are essential for MEAS. Further, we demonstrate that the hnRNP PTBP1 binds the ISS and is a regulator of TCF3 AS. We also demonstrate that hnRNP H1 and PTBP1 regulate TCF3 AS reciprocally, and that position-dependent interactions between these factors are essential for proper TCF3 MEAS. Our study provides a new model in which MEAS is regulated by cooperative actions of distinct hnRNPs bound to ISSs and ESSs.
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http://dx.doi.org/10.1261/rna.072298.119 | DOI Listing |
Front Oncol
August 2025
Department of Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, United States.
Introduction: Metastatic colorectal cancer (mCRC) exhibits significant heterogeneity in molecular profiles, influencing treatment response and patient outcomes. Mutations in v-raf murine sarcoma viral oncogene homolog B1 () and rat sarcoma () family genes are commonly observed in mCRC. Though originally thought to be mutually exclusive, recent data have shown that patients may present with concomitant and mutations, posing unique challenges and implications for clinical management.
View Article and Find Full Text PDFRev Cardiovasc Med
August 2025
Cardiology Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón, CIBERCV, 28007 Madrid, Spain.
Stress cardiomyopathy/Takotsubo syndrome (TTS) is a transient cardiac condition characterized by sudden and reversible left ventricular dysfunction, typically triggered by emotional or physical stress. The international TTS (InterTAK) score predicts the probability of suffering from TTS. However, the diagnostic algorithm includes three mutually exclusive diagnoses: acute coronary syndrome (ACS), TTS, and acute infectious myocarditis.
View Article and Find Full Text PDFJ Manipulative Physiol Ther
September 2025
Clinical & Health Services Research, Southern California University of Health Sciences, Whittier, California.
Objective: The purpose of this study was to evaluate the risk of selected adverse outcomes for older adults with a new episode of neck pain (NP) receiving chiropractic care compared to those receiving primary medical care with Prescription Drug Therapy (PDT) or primary care without medication.
Methods: Through analysis of Medicare claims data, we designed a retrospective cohort study including 291 604 patients with a new office visit for NP in 2019. We developed 3 mutually exclusive exposure groups: the Chiropractic Manipulative Therapy (CMT) group received spinal manipulative therapy from a chiropractor with no primary care visits; the PDT group visited primary care and filled an analgesic prescription within 7 days without chiropractic care, and the Primary Care Only (PCO) group visited primary care without chiropractic care or analgesic prescriptions.
Nicotine Tob Res
September 2025
College of Public Health, University of Nebraska Medical Center, Omaha, NE, United States.
Introduction: Nicotine pouches (NPs) are an emerging nicotine delivery system. Understanding nicotine and toxicant exposure among NP users compared with users of other tobacco products and non-users is critical for informing public health strategies.
Methods: Data (n = 4527) were drawn from the Population Assessment of Tobacco and Health Study Wave 7 (2022-2023).
Adv Mater
September 2025
Center for Renewable Energy and Storage Technologies (CREST), King Abdullah University of Science and Technology (KAUST), Thuwal, 23955-6900, Saudi Arabia.
The orientation of MXene flakes has received increasing research attention as it plays a critical role in determining the performance of MXene-based assemblies. Engineering MXene flakes into horizontal or vertical orientations can offer distinct advantages such as higher electrical conductivity, higher mechanical strength, and more efficient ion/molecule transport across the flakes. However, the benefits of horizontal and vertical orientations are mutually exclusive, and both of them possess structural symmetry that restricts their ability for stimuli-responsive deformation.
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