M6A-facilitated hippocampal learning and memory through Ythdf1
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA417392 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7146500.fastq.gz | Fastqsanger.gz | |||
| SRR7146510.fastq.gz | Fastqsanger.gz | |||
| SRR7146520.fastq.gz | Fastqsanger.gz | |||
| SRR7146501.fastq.gz | Fastqsanger.gz | |||
| SRR7146511.fastq.gz | Fastqsanger.gz |
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Project description:The N6-methyladenosine (m6A) mRNA modification and the mitochondrial respiratory chain (MRC) hold paramount importance in the advancement of MASLD. This study thoroughly investigates the relationship and impact of m6A mRNA modification and mitochondrial function in the progression of MASLD. Here we report that the mRNA and protein levels of mitochondrial respiratory chain (MRC) subunits showed inconsistent trends in vivo experiments. Abnormal m6A modification and mitochondrial dysfunction in MASLD were attributed to the upregulation of methyltransferase like 3 (Mettl3) and the downregulation of YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) induced by high-fat foods. Mettl3 promoted the MRC's function. However, knockout of the reader protein YTHDF1, which plays a crucial role in the m6A modification process, counteracted the effect of Mettl3 and suppressed MRC. In MASLD, damage to the MRC may be regulated by the Mettl3-m6A-YTHDF1 complex axis, especially by the role of YTHDF1. Our research has offered a novel perspective on the involvement of m6A mRNA methylation in the pathogenesis of MASLD.
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Project description:N6-methyladenosine (m6A) RNA methylation is implicated in the progression of multiple cancers via influencing mRNA modification. Intersection of RNA-seq, Methylated RNA immune-precipitation (MeRIP)-seq, co-immunoprecipitation, RNA pull-down and MeRIP-PCR were used to identify YTHDF1- modified USP14 and its m6A levels in GC cells. Intersection assays revealed that YTHDF1 promoted USP14 protein translation in an m6A-dependent manner. Our data suggested that m6A reader YTHDF1 facilitated tumorigenesis and metastasis of GC by promoting USP14 protein translation and might act as a clinical therapy for GC.
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Project description:Neuroplasticity and synaptic dysfunction are central to depression, yet the underlying mechanisms remain poorly understood. While m6A and its reader YTHDF1 regulate mRNA translation, neuroplasticity and learning behaviors, their role in affective disorders such as depression remains unexplored. This study identifies YTHDF1 as a key regulator of depression pathogenesis. Genetic deletion of YTHDF1 in mice caused anterior cingulate cortex (ACC) hyperactivity, heightened social stress sensitivity, and anxiodepressive-like behaviors after acute social stress. Using multi-omic approaches, we uncovered a critical role for actin cytoskeleton dynamics and identified cyclase-associated protein 1 (CAP1) as a downstream effector of YTHDF1. Loss of YTHDF1 reduced CAP1 expression from early postnatal stages, resulting in F-actin accumulation, impaired synaptic function, and behavioral deficits. Strikingly, early postnatal YTHDF1 re-expression in the ACC restored CAP1 levels, synaptic integrity, and reversed depressive-like phenotypes. These findings establish the m6A/YTHDF1/CAP1 axis as a critical pathway regulating synaptic function and depression.
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Project description:Neuroplasticity and synaptic dysfunction are central to depression, yet the underlying mechanisms remain poorly understood. While m6A and its reader YTHDF1 regulate mRNA translation, neuroplasticity and learning behaviors, their role in affective disorders such as depression remains unexplored. This study identifies YTHDF1 as a key regulator of depression pathogenesis. Genetic deletion of YTHDF1 in mice caused anterior cingulate cortex (ACC) hyperactivity, heightened social stress sensitivity, and anxiodepressive-like behaviors after acute social stress. Using multi-omic approaches, we uncovered a critical role for actin cytoskeleton dynamics and identified cyclase-associated protein 1 (CAP1) as a downstream effector of YTHDF1. Loss of YTHDF1 reduced CAP1 expression from early postnatal stages, resulting in F-actin accumulation, impaired synaptic function, and behavioral deficits. Strikingly, early postnatal YTHDF1 re-expression in the ACC restored CAP1 levels, synaptic integrity, and reversed depressive-like phenotypes. These findings establish the m6A/YTHDF1/CAP1 axis as a critical pathway regulating synaptic function and depression.
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Project description:Neuroplasticity and synaptic dysfunction are central to depression, yet the underlying mechanisms remain poorly understood. While m6A and its reader YTHDF1 regulate mRNA translation, neuroplasticity and learning behaviors, their role in affective disorders such as depression remains unexplored. This study identifies YTHDF1 as a key regulator of depression pathogenesis. Genetic deletion of YTHDF1 in mice caused anterior cingulate cortex (ACC) hyperactivity, heightened social stress sensitivity, and anxiodepressive-like behaviors after acute social stress. Using multi-omic approaches, we uncovered a critical role for actin cytoskeleton dynamics and identified cyclase-associated protein 1 (CAP1) as a downstream effector of YTHDF1. Loss of YTHDF1 reduced CAP1 expression from early postnatal stages, resulting in F-actin accumulation, impaired synaptic function, and behavioral deficits. Strikingly, early postnatal YTHDF1 re-expression in the ACC restored CAP1 levels, synaptic integrity, and reversed depressive-like phenotypes. These findings establish the m6A/YTHDF1/CAP1 axis as a critical pathway regulating synaptic function and depression.
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Project description:N6-methyladenosine (m6A) modification has been implicated in many cell processes and diseases. YTHDF1, a translation-facilitating m6A reader, is not previously shown to be related to allergic airway inflammation. Here, we report that YTHDF1 is highly expressed in allergic airway epithelial cells (AECs) and asthmatic patients, and influences proinflammatory responses. CLOCK, a subunit of the circadian clock pathway, is the direct target of YTHDF1. YTHDF1 augments CLOCK translation in an m6A-dependent manner. Allergens enhance the liquid‒liquid phase separation (LLPS) of YTHDF1 and drive the formation of a complex comprising dimeric YTHDF1 and CLOCK mRNA, which is distributed to stress granules (SGs). Moreover, YTHDF1 strongly activates NLRP3 inflammasome production and IL-1β secretion, leading to airway inflammatory responses, but these phenotypes are abolished by deleting CLOCK. These findings demonstrate that YTHDF1 is an important regulator of asthmatic airway inflammation, suggesting a potential therapeutic target for allergic airway inflammation.
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