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Alternative splicing is prevalent in plants, but little is known about its regulation in the context of developmental and signaling pathways. We describe here a new factor that influences pre-messengerRNA (mRNA) splicing and is essential for embryonic development in Arabidopsis thaliana. This factor was retrieved in a genetic screen that identified mutants impaired in expression of an alternatively spliced GFP reporter gene. In addition to the known spliceosomal component PRP8, the screen recovered Arabidopsis RTF2 (AtRTF2), a previously uncharacterized, evolutionarily conserved protein containing a replication termination factor 2 (Rtf2) domain. A homozygous null mutation in AtRTF2 is embryo lethal, indicating that AtRTF2 is an essential protein. Quantitative RT-PCR demonstrated that impaired expression of GFP in atrtf2 and prp8 mutants is due to inefficient splicing of the GFP pre-mRNA. A genome-wide analysis using RNA sequencing indicated that 13-16% of total introns are retained to a significant degree in atrtf2 mutants. Considering these results and previous suggestions that Rtf2 represents an ubiquitin-related domain, we discuss the possible role of AtRTF2 in ubiquitin-based regulation of pre-mRNA splicing.
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http://dx.doi.org/10.1534/genetics.115.176438 | DOI Listing |
PLoS One
September 2025
Department of Hygiene, Kawasaki Medical School, Kurashiki, Japan.
T-cell therapies have proven to be a promising treatment option for cancer patients in recent years, especially in the case of chimeric antigen receptor (CAR)-T cell therapy. However, the therapy is associated with insufficient activation of T cells or poor persistence in the patient's body, which leads to incomplete elimination of cancer cells, recurrence, and genotoxicity. By extracting the splice element of PD-1 pre-mRNA using biology based on CRISPR/dCas13 in this study, our ultimate goal is to overcome the above-mentioned challenges in the future.
View Article and Find Full Text PDFJ Assoc Res Otolaryngol
September 2025
Department of Anesthesiology, Northwestern University Feinberg School of Medicine, Chicago, IL, 60611, USA.
Purpose: The mammalian cochlea has two types of low abundance and highly specialized inner (IHC) and outer (OHC) mechanosensory hair cells. Their malfunction or death is a common cause of congenital and acquired deafness. IHCs and OHCs exhibit different transcriptomes during development.
View Article and Find Full Text PDFJ Neurochem
September 2025
State Key Laboratory of Oral Diseases & National Center for Stomatology & National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Orofacial neuropathic pain, a debilitating condition associated with trigeminal nerve injury, is often characterized by allodynia. N-methyl-d-aspartate receptors (NMDARs), particularly the GluN1 subunit, play a central role in mediating this pain. The GluN1 subunit undergoes alternative splicing at exon 5, generating isoforms GluN1a (lacking the exon 5-encoded N1 cassette) and GluN1b (retaining the N1 cassette), which have distinct functional roles.
View Article and Find Full Text PDFFront Genet
August 2025
Department of Basic Medicine, School of Medicine, Jingchu University of Technology, Jingmen, China.
Introduction: Mediator of RNA polymerase II transcription subunit 25 (), a crucial component of the transcriptional coactivator complex, plays a significant role in the transcription of most RNA polymerase II-dependent genes. Mutations in have been linked to various genetic syndromes, including Basel-Vanagaite-Smirin-Yosef Syndrome (BVSYS) and Intellectual Disability (ID). This study elucidated the molecular mechanism through which compound heterozygous mutations in the gene impaired pre-mRNA splicing, ultimately causing BVSYS.
View Article and Find Full Text PDFMol Ther Nucleic Acids
September 2025
Department of Synthetic Biology and Immunology, National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia.
Loss-of-function mutations in the gene cause β-catenin deficiency, resulting in CTNNB1 syndrome, a rare neurodevelopmental disorder characterized by motor and cognitive impairments. Given the wide variety of mutations across and its dosage sensitivity, a mutation-independent therapeutic approach that preserves endogenous gene regulation is critically needed. This study introduces spliceosome-mediated RNA -splicing as a novel approach to restore β-catenin production.
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