Purpose: Mediator is a multiprotein complex that allows the transfer of genetic information from DNA binding proteins to the RNA polymerase II during transcription initiation. MED12L is a subunit of the kinase module, which is one of the four subcomplexes of the mediator complex. Other subunits of the kinase module have been already implicated in intellectual disability, namely MED12, MED13L, MED13, and CDK19.
Methods: We describe an international cohort of seven affected individuals harboring variants involving MED12L identified by array CGH, exome or genome sequencing.
Results: All affected individuals presented with intellectual disability and/or developmental delay, including speech impairment. Other features included autism spectrum disorder, aggressive behavior, corpus callosum abnormality, and mild facial morphological features. Three individuals had a MED12L deletion or duplication. The other four individuals harbored single-nucleotide variants (one nonsense, one frameshift, and two splicing variants). Functional analysis confirmed a moderate and significant alteration of RNA synthesis in two individuals.
Conclusion: Overall data suggest that MED12L haploinsufficiency is responsible for intellectual disability and transcriptional defect. Our findings confirm that the integrity of this kinase module is a critical factor for neurological development.
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http://dx.doi.org/10.1038/s41436-019-0557-3 | DOI Listing |
PLoS Pathog
December 2024
Newcastle University Biosciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, United Kingdom.
The Hog1 stress-activated protein kinase (SAPK) is a key mediator of stress resistance and virulence in Candida albicans. Hog1 activation via phosphorylation of the canonical TGY motif is mediated by the Pbs2 MAPKK, which itself is activated by the Ssk2 MAPKKK. Although this three-tiered SAPK signalling module is well characterised, it is unclear how Hog1 activation is regulated in response to different stresses.
View Article and Find Full Text PDFCarcinogenesis
December 2024
Division of Hematology, Second Xiangya Hospital, Central South University, No.139th Renmin Middle Road, Changsha, 410011, Hunan, China.
Chronic myeloid leukemia (CML) is a malignant hyperplastic tumor that originats from pluripotent hematopoietic stem cells in the bone marrow. The introduction of tyrosine kinase inhibitors (TKIs) has significantly improved the survival rates of CML patients. This study aimed to identify immune-related genes (IRGs) associated with the response to imatinib therapy in CML.
View Article and Find Full Text PDFPlant Physiol
December 2024
Key Laboratory of Bio-resource and Eco-environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610064, China.
Soil salinization threatens global crop production. Here, we report that a receptor-like cytoplasmic kinase (RLCK), CALMODULIN-BINDING RECEPTOR-LIKE CYTOPLASMIC KINASE 3 (CRCK3), plays an essential role in plant salt tolerance via CATALASE 2 (CAT2), a hydrogen peroxide (H2O2)-scavenging enzyme in Arabidopsis (Arabidopsis thaliana). CRCK3 was induced by salt stress, and its knockout mutant displayed a salt-sensitive phenotype compared to wild-type (WT) plants.
View Article and Find Full Text PDFPlant Physiol
December 2024
Key Laboratory of Biology and Genetic Improvement of Horticultural Crops (Northeast Region), Ministry of Agriculture and Rural Affairs/Northeast Agricultural University, Harbin, 150030, China.
Pumpkin (Cucurbita maxima D.) is typically monoecious with individual male and female flowers, and its yield is associated with the degree of femaleness, i.e.
View Article and Find Full Text PDFmSphere
December 2024
Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
Unlabelled: The eukaryotic CCR4-NOT deadenylase complex is a highly conserved regulator of mRNA metabolism that influences the expression of the complete transcriptome, representing a prime target for a generalist bacterial pathogen. We show that a translocated bacterial effector protein, PieF (Lpg1972) of , directly interacts with the CNOT7/8 nuclease module of CCR4-NOT, with a dissociation constant in the low nanomolar range. PieF is a robust inhibitor of the DEDD-type nuclease, CNOT7, acting in a stoichiometric, dose-dependent manner.
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