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1.
Nat Rev Mol Cell Biol ; 23(3): 185-203, 2022 03.
Article in English | MEDLINE | ID: mdl-34707241

ABSTRACT

Since the discovery of eukaryotic small RNAs as the main effectors of RNA interference in the late 1990s, diverse types of endogenous small RNAs have been characterized, most notably microRNAs, small interfering RNAs (siRNAs) and PIWI-interacting RNAs (piRNAs). These small RNAs associate with Argonaute proteins and, through sequence-specific gene regulation, affect almost every major biological process. Intriguing features of small RNAs, such as their mechanisms of amplification, rapid evolution and non-cell-autonomous function, bestow upon them the capacity to function as agents of intercellular communications in development, reproduction and immunity, and even in transgenerational inheritance. Although there are many types of extracellular small RNAs, and despite decades of research, the capacity of these molecules to transmit signals between cells and between organisms is still highly controversial. In this Review, we discuss evidence from different plants and animals that small RNAs can act in a non-cell-autonomous manner and even exchange information between species. We also discuss mechanistic insights into small RNA communications, such as the nature of the mobile agents, small RNA signal amplification during transit, signal perception and small RNA activity at the destination.


Subject(s)
Argonaute Proteins , MicroRNAs , RNA, Small Interfering , Animals , Argonaute Proteins/genetics , Argonaute Proteins/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Plants/genetics , Plants/metabolism , RNA Interference , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism
2.
Annu Rev Cell Dev Biol ; 35: 407-431, 2019 10 06.
Article in English | MEDLINE | ID: mdl-31403819

ABSTRACT

A large and significant portion of eukaryotic transcriptomes consists of noncoding RNAs (ncRNAs) that have minimal or no protein-coding capacity but are functional. Diverse ncRNAs, including both small RNAs and long ncRNAs (lncRNAs), play essential regulatory roles in almost all biological processes by modulating gene expression at the transcriptional and posttranscriptional levels. In this review, we summarize the current knowledge of plant small RNAs and lncRNAs, with a focus on their biogenesis, modes of action, local and systemic movement, and functions at the nexus of plant development and environmental responses. The complex connections among small RNAs, lncRNAs, and small peptides in plants are also discussed, along with the challenges of identifying and investigating new classes of ncRNAs.


Subject(s)
Plant Development/genetics , Plants/genetics , RNA, Long Noncoding/metabolism , RNA, Plant/metabolism , Stress, Physiological/genetics , Gene Expression Regulation, Plant/genetics , Gene Expression Regulation, Plant/physiology , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , RNA, Long Noncoding/genetics , RNA, Plant/genetics , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism
3.
Cell ; 153(3): 562-74, 2013 Apr 25.
Article in English | MEDLINE | ID: mdl-23622241

ABSTRACT

Translation inhibition is a major but poorly understood mode of action of microRNAs (miRNAs) in plants and animals. In particular, the subcellular location where this process takes place is unknown. Here, we show that the translation inhibition, but not the mRNA cleavage activity, of Arabidopsis miRNAs requires ALTERED MERISTEM PROGRAM1 (AMP1). AMP1 encodes an integral membrane protein associated with endoplasmic reticulum (ER) and ARGONAUTE1, the miRNA effector and a peripheral ER membrane protein. Large differences in polysome association of miRNA target RNAs are found between wild-type and the amp1 mutant for membrane-bound, but not total, polysomes. This, together with AMP1-independent recruitment of miRNA target transcripts to membrane fractions, shows that miRNAs inhibit the translation of target RNAs on the ER. This study demonstrates that translation inhibition is an important activity of plant miRNAs, reveals the subcellular location of this activity, and uncovers a previously unknown function of the ER.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/metabolism , Carboxypeptidases/metabolism , Endoplasmic Reticulum/metabolism , MicroRNAs/metabolism , RNA, Plant/metabolism , Arabidopsis/genetics , Arabidopsis/growth & development , Arabidopsis Proteins/genetics , Carboxypeptidases/genetics , Genetic Pleiotropy , Mutation , Polyribosomes/metabolism , Protein Biosynthesis , RNA, Messenger/metabolism
4.
Plant Cell ; 36(7): 2668-2688, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38581433

ABSTRACT

The style and stigma at the apical gynoecium are crucial for flowering plant reproduction. However, the mechanisms underlying specification of the apical gynoecium remain unclear. Here, we demonstrate that Class II TEOSINTE BRANCHED 1/CYCLOIDEA/PCF (TCP) transcription factors are critical for apical gynoecium specification in Arabidopsis (Arabidopsis thaliana). The septuple tcp2 tcp3 tcp4 tcp5 tcp10 tcp13 tcp17 (tcpSEP) and duodecuple tcp2 tcp3 tcp4 tcp5 tcp10 tcp13 tcp17 tcp24 tcp1 tcp12 tcp18 tcp16 (tcpDUO) mutants produce narrower and longer styles, while disruption of TCPs and CRABS CLAW (CRC) or NGATHAs (NGAs) in tcpDUO crc or tcpDUO nga1 nga2 nga4 causes the apical gynoecium to be replaced by lamellar structures with indeterminate growth. TCPs are predominantly expressed in the apex of the gynoecium. TCP4 interacts with CRC to synergistically upregulate the expression level of NGAs, and NGAs further form high-order complexes to control the expression of auxin-related genes in the apical gynoecium by directly interacting with TCP4. Our findings demonstrate that TCP4 physically associates with CRC and NGAs to control auxin biosynthesis in forming fine structures of the apical gynoecium.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Flowers , Gene Expression Regulation, Plant , Transcription Factors , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Flowers/genetics , Flowers/metabolism , Flowers/growth & development , Mutation
5.
Plant Cell ; 35(8): 2750-2772, 2023 08 02.
Article in English | MEDLINE | ID: mdl-37144845

ABSTRACT

RNA-binding proteins (RBPs) play critical roles in posttranscriptional gene regulation. Current methods of systematically profiling RBPs in plants have been predominantly limited to proteins interacting with polyadenylated (poly(A)) RNAs. We developed a method called plant phase extraction (PPE), which yielded a highly comprehensive RNA-binding proteome (RBPome), uncovering 2,517 RBPs from Arabidopsis (Arabidopsis thaliana) leaf and root samples with a highly diverse array of RNA-binding domains. We identified traditional RBPs that participate in various aspects of RNA metabolism and a plethora of nonclassical proteins moonlighting as RBPs. We uncovered constitutive and tissue-specific RBPs essential for normal development and, more importantly, revealed RBPs crucial for salinity stress responses from a RBP-RNA dynamics perspective. Remarkably, 40% of the RBPs are non-poly(A) RBPs that were not previously annotated as RBPs, signifying the advantage of PPE in unbiasedly retrieving RBPs. We propose that intrinsically disordered regions contribute to their nonclassical binding and provide evidence that enzymatic domains from metabolic enzymes have additional roles in RNA binding. Taken together, our findings demonstrate that PPE is an impactful approach for identifying RBPs from complex plant tissues and pave the way for investigating RBP functions under different physiological and stress conditions at the posttranscriptional level.


Subject(s)
Arabidopsis , Proteome , Proteome/genetics , Proteome/metabolism , Plants/genetics , Arabidopsis/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , RNA
6.
Plant Cell ; 35(6): 2208-2231, 2023 05 29.
Article in English | MEDLINE | ID: mdl-36943781

ABSTRACT

The macronutrient phosphorus is essential for plant growth and development. Plants have evolved multiple strategies to increase the efficiency of phosphate (Pi) acquisition to protect themselves from Pi starvation. However, the crosstalk between Pi homeostasis and plant development remains to be explored. Here, we report that overexpressing microRNA399 (miR399) in maize (Zea mays) is associated with premature senescence after pollination. Knockout of ZmPHO2 (Phosphate 2), a miR399 target, resulted in a similar premature senescence phenotype. Strikingly, we discovered that INDETERMINATE1 (ID1), a floral transition regulator, inhibits the transcription of ZmMIR399 genes by directly binding to their promoters, alleviating the repression of ZmPHO2 by miR399 and ultimately contributing to the maintenance of Pi homeostasis in maize. Unlike ZmMIR399 genes, whose expression is induced by Pi deficiency, ID1 expression was independent of the external inorganic orthophosphate status, indicating that ID1 is an autonomous regulator of Pi homeostasis. Furthermore, we show that ZmPHO2 was under selection during maize domestication and cultivation, resulting in a more sensitive response to Pi starvation in temperate maize than in tropical maize. Our study reveals a direct functional link between Pi-deprivation sensing by the miR399-ZmPHO2 regulatory module and plant developmental regulation by ID1.


Subject(s)
Phosphates , Zea mays , Zea mays/genetics , Zea mays/metabolism , Phosphates/metabolism , Phosphorus/metabolism , Plants/metabolism , Homeostasis/genetics , Gene Expression Regulation, Plant/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Roots/metabolism
7.
PLoS Genet ; 19(3): e1010450, 2023 03.
Article in English | MEDLINE | ID: mdl-36888599

ABSTRACT

microRNAs (miRNAs) regulate target gene expression through their ARGONAUTE (AGO) effector protein, mainly AGO1 in Arabidopsis thaliana. In addition to the highly conserved N, PAZ, MID and PIWI domains with known roles in RNA silencing, AGO1 contains a long, unstructured N-terminal extension (NTE) of little-known function. Here, we show that the NTE is indispensable for the functions of Arabidopsis AGO1, as a lack of the NTE leads to seedling lethality. Within the NTE, the region containing amino acids (a.a.) 91 to 189 is essential for rescuing an ago1 null mutant. Through global analyses of small RNAs, AGO1-associated small RNAs, and miRNA target gene expression, we show that the region containing a.a. 91-189 is required for the loading of miRNAs into AGO1. Moreover, we show that reduced nuclear partitioning of AGO1 did not affect its profiles of miRNA and ta-siRNA association. Furthermore, we show that the 1-to-90a.a. and 91-to-189a.a. regions of the NTE redundantly promote the activities of AGO1 in the biogenesis of trans-acting siRNAs. Together, we report novel roles of the NTE of Arabidopsis AGO1.


Subject(s)
Arabidopsis Proteins , Arabidopsis , MicroRNAs , Arabidopsis/genetics , Arabidopsis/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Arabidopsis Proteins/metabolism , RNA, Small Interfering/genetics , RNA Interference , Argonaute Proteins/genetics , Argonaute Proteins/metabolism
8.
Proc Natl Acad Sci U S A ; 120(15): e2301081120, 2023 04 11.
Article in English | MEDLINE | ID: mdl-37011204

ABSTRACT

Ribosome biogenesis is essential for protein synthesis in gene expression. Yeast eIF5B has been shown biochemically to facilitate 18S ribosomal RNA (rRNA) 3' end maturation during late-stage 40S ribosomal subunit assembly and gate the transition from translation initiation to elongation. But the genome-wide effects of eIF5B have not been studied at the single-nucleotide resolution in any organism, and 18S rRNA 3' end maturation is poorly understood in plants. Arabidopsis HOT3/eIF5B1 was found to promote development and heat stress acclimation by translational regulation, but its molecular function remained unknown. Here, we show that HOT3 is a late-stage ribosome biogenesis factor that facilitates 18S rRNA 3' end processing and is a translation initiation factor that globally impacts the transition from initiation to elongation. By developing and implementing 18S-ENDseq, we revealed previously unknown events in 18S rRNA 3' end maturation or metabolism. We quantitatively defined processing hotspots and identified adenylation as the prevalent nontemplated RNA addition at the 3' ends of pre-18S rRNAs. Aberrant 18S rRNA maturation in hot3 further activated RNA interference to generate RDR1- and DCL2/4-dependent risiRNAs mainly from a 3' portion of 18S rRNA. We further showed that risiRNAs in hot3 were predominantly localized in ribosome-free fractions and were not responsible for the 18S rRNA maturation or translation initiation defects in hot3. Our study uncovered the molecular function of HOT3/eIF5B1 in 18S rRNA maturation at the late 40S assembly stage and revealed the regulatory crosstalk among ribosome biogenesis, messenger RNA (mRNA) translation initiation, and siRNA biogenesis in plants.


Subject(s)
Arabidopsis , RNA, Ribosomal, 18S/genetics , RNA, Ribosomal, 18S/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , RNA Interference , Ribosomes/metabolism , Protein Biosynthesis , Saccharomyces cerevisiae/metabolism , RNA Precursors/genetics
9.
Plant Physiol ; 195(3): 1954-1968, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38466155

ABSTRACT

Due to climate change, drought has become a major threat to rice (Oryza sativa L.) growth and yield worldwide. Understanding the genetic basis of drought tolerance in rice is therefore of great importance. Here, we identified a microRNA, miR1432, which regulates rice drought tolerance by targeting the CALMODULIN-LIKE2 (OsCaML2) gene. Mutation of MIR1432 or suppression of miR1432 expression significantly impaired seed germination and seedling growth under drought-stress conditions. Molecular analysis demonstrated that miR1432 affected rice drought tolerance by directly targeting OsCaML2, which encodes an EF-hand chiral calcium-binding protein. Overexpression of a miR1432-resistant form of OsCaML2 (OEmCaML2) phenocopied the mir1432 mutant and miR1432 suppression plants. Furthermore, the suppression of miR1432 severely affected the expression of genes involved in responses to stimulation, metabolism and signal transduction, especially the mitogen-activated protein kinase (MAPK) pathway and hormone transduction pathway in rice under drought stress. Thus, our findings show that the miR1432-OsCaML2 module plays an important role in the regulation of rice drought tolerance, suggesting its potential utilization in developing molecular breeding strategies that improve crop drought tolerance.


Subject(s)
Calmodulin , Droughts , Gene Expression Regulation, Plant , MicroRNAs , Oryza , Plant Proteins , Stress, Physiological , Oryza/genetics , Oryza/physiology , MicroRNAs/genetics , MicroRNAs/metabolism , Calmodulin/genetics , Calmodulin/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Stress, Physiological/genetics , Mutation/genetics , Plants, Genetically Modified , Seedlings/genetics , Seedlings/physiology , Seedlings/growth & development , Adaptation, Physiological/genetics , Germination/genetics
10.
Plant Cell ; 34(1): 503-513, 2022 01 20.
Article in English | MEDLINE | ID: mdl-34648025

ABSTRACT

Epigenomics is the study of molecular signatures associated with discrete regions within genomes, many of which are important for a wide range of nuclear processes. The ability to profile the epigenomic landscape associated with genes, repetitive regions, transposons, transcription, differential expression, cis-regulatory elements, and 3D chromatin interactions has vastly improved our understanding of plant genomes. However, many epigenomic and single-cell genomic assays are challenging to perform in plants, leading to a wide range of data quality issues; thus, the data require rigorous evaluation prior to downstream analyses and interpretation. In this commentary, we provide considerations for the evaluation of plant epigenomics and single-cell genomics data quality with the aim of improving the quality and utility of studies using those data across diverse plant species.


Subject(s)
Epigenomics , Regulatory Sequences, Nucleic Acid , Chromatin/genetics , Genome, Plant/genetics , Plants/genetics , Quality Control
11.
Cereb Cortex ; 34(7)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39030743

ABSTRACT

Nouns and verbs are fundamental grammatical building blocks of languages. A key question is whether and where the noun-verb division was represented in the brain. Previous studies mainly used univariate analyses to examine this issue. However, the interpretation of activated brain regions in univariate analyses may be confounded with general cognitive processing and/or confounding variables. We addressed these limitations by using partial representation similarity analysis (RSA) of Chinese nouns and verbs with different levels of imageability. Participants were asked to complete the 1-back grammatical class probe (GCP; an explicit measure) and the 1-back word probe (WP; an implicit measure) tasks while undergoing functional magnetic resonance imaging. RSA results showed that the activation pattern in the left posterior middle temporal gyrus (LpMTG) was significantly correlated with the grammatical class representational dissimilarity matrix in the GCP task after eliminating the potential confounding variables. Moreover, the LpMTG did not overlap with the frontal-parietal regions that were activated by verbs vs. nouns or the task effect (CRP vs. WP) in univariate analyses. These results highlight the role of LpMTG in distinguishing nouns from verbs rather than general cognitive processing.


Subject(s)
Brain Mapping , Magnetic Resonance Imaging , Temporal Lobe , Humans , Male , Temporal Lobe/physiology , Temporal Lobe/diagnostic imaging , Female , Magnetic Resonance Imaging/methods , Brain Mapping/methods , Young Adult , Adult , Language , Semantics , Functional Laterality/physiology
12.
Proc Natl Acad Sci U S A ; 119(41): e2208415119, 2022 10 11.
Article in English | MEDLINE | ID: mdl-36191209

ABSTRACT

MicroRNAs (miRNAs) play an essential role in plant growth and development, and as such, their biogenesis is fine-tuned via regulation of the core microprocessor components. Here, we report that Arabidopsis AAR2, a homolog of a U5 snRNP assembly factor in yeast and humans, not only acts in splicing but also promotes miRNA biogenesis. AAR2 interacts with the microprocessor component hyponastic leaves 1 (HYL1) in the cytoplasm, nucleus, and dicing bodies. In aar2 mutants, abundance of nonphosphorylated HYL1, the active form of HYL1, and the number of HYL1-labeled dicing bodies are reduced. Primary miRNA (pri-miRNA) accumulation is compromised despite normal promoter activities of MIR genes in aar2 mutants. RNA decay assays show that the aar2-1 mutation leads to faster degradation of pri-miRNAs in a HYL1-dependent manner, which reveals a previously unknown and negative role of HYL1 in miRNA biogenesis. Taken together, our findings reveal a dual role of AAR2 in miRNA biogenesis and pre-messenger RNA splicing.


Subject(s)
Arabidopsis Proteins , Arabidopsis , MicroRNAs , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Eukaryota/genetics , Gene Expression Regulation, Plant , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , RNA Processing, Post-Transcriptional , RNA Splicing Factors/genetics , RNA, Messenger/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism , Ribonucleoprotein, U5 Small Nuclear/genetics
13.
Plant J ; 116(1): 144-160, 2023 10.
Article in English | MEDLINE | ID: mdl-37415266

ABSTRACT

RCF1 is a highly conserved DEAD-box RNA helicase found in yeast, plants, and mammals. Studies about the functions of RCF1 in plants are limited. Here, we uncovered the functions of RCF1 in Arabidopsis thaliana as a player in pri-miRNA processing and splicing, as well as in pre-mRNA splicing. A mutant with miRNA biogenesis defects was isolated, and the defect was traced to a recessive point mutation in RCF1 (rcf1-4). We show that RCF1 promotes D-body formation and facilitates the interaction between pri-miRNAs and HYL1. Finally, we show that intron-containing pri-miRNAs and pre-mRNAs exhibit a global splicing defect in rcf1-4. Together, this work uncovers roles for RCF1 in miRNA biogenesis and RNA splicing in Arabidopsis.


Subject(s)
Arabidopsis Proteins , Arabidopsis , MicroRNAs , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , DEAD-box RNA Helicases/genetics , Gene Expression Regulation, Plant/genetics , MicroRNAs/genetics , MicroRNAs/metabolism , RNA Processing, Post-Transcriptional , RNA Splicing/genetics , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism
14.
J Clin Immunol ; 44(5): 124, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758476

ABSTRACT

PURPOSES: STAT1 is a transduction and transcriptional regulator that functions within the classical JAK/STAT pathway. In addition to chronic mucocutaneous candidiasis, bacterial infections are a common occurrence in patients with STAT1 gain-of-function (GOF) mutations. These patients often exhibit skewing of B cell subsets; however, the impact of STAT1-GOF mutations on B cell-mediated humoral immunity remains largely unexplored. It is also unclear whether these patients with IgG within normal range require regular intravenous immunoglobulin (IVIG) therapy. METHODS: Eleven patients (harboring nine different STAT1-GOF mutations) were enrolled. Reporter assays and immunoblot analyses were performed to confirm STAT1 mutations. Flow cytometry, deep sequencing, ELISA, and ELISpot were conducted to assess the impact of STAT1-GOF on humoral immunity. RESULTS: All patients exhibited increased levels of phospho-STAT1 and total STAT1 protein, with two patients carrying novel mutations. In vitro assays showed that these two novel mutations were GOF mutations. Three patients with normal total IgG levels received regular IVIG infusions, resulting in effective control of bacterial infections. Four cases showed impaired affinity and specificity of pertussis toxin-specific antibodies, accompanied by reduced generation of class-switched memory B cells. Patients also had a disrupted immunoglobulin heavy chain (IGH) repertoire, coupled with a marked reduction in the somatic hypermutation frequency of switched Ig transcripts. CONCLUSION: STAT1-GOF mutations disrupt B cell compartments and skew IGH characteristics, resulting in impaired affinity and antigen-specificity of antibodies and recurrent bacterial infections. Regular IVIG therapy can control these infections in patients, even those with normal total IgG levels.


Subject(s)
B-Lymphocytes , Bacterial Infections , Gain of Function Mutation , Immunoglobulins, Intravenous , STAT1 Transcription Factor , Humans , STAT1 Transcription Factor/genetics , Bacterial Infections/immunology , Bacterial Infections/genetics , Female , Male , Child , Immunoglobulins, Intravenous/therapeutic use , B-Lymphocytes/immunology , Adult , Immunoglobulin G/immunology , Immunoglobulin G/blood , Child, Preschool , Adolescent , Young Adult , Immunity, Humoral
15.
Plant Cell ; 33(5): 1530-1553, 2021 07 02.
Article in English | MEDLINE | ID: mdl-33570655

ABSTRACT

The coordinated development of sporophytic and gametophytic tissues is essential for proper ovule patterning and fertility. However, the mechanisms regulating their integrated development remain poorly understood. Here, we report that the Swi2/Snf2-Related1 (SWR1) chromatin-remodeling complex acts with the ERECTA receptor kinase-signaling pathway to control female gametophyte and integument growth in Arabidopsis thaliana by inhibiting transcription of the microRNA gene MIR398c in early-stage megagametogenesis. Moreover, pri-miR398c is transcribed in the female gametophyte but is then translocated to and processed in the ovule sporophytic tissues. Together, SWR1 and ERECTA also activate ARGONAUTE10 (AGO10) expression in the chalaza; AGO10 sequesters miR398, thereby ensuring the expression of three AGAMOUS-LIKE (AGL) genes (AGL51, AGL52, and AGL78) in the female gametophyte. In the context of sexual organ morphogenesis, these findings suggest that the spatiotemporal control of miRNA biogenesis, resulting from coordination between chromatin remodeling and cell signaling, is essential for proper ovule development in Arabidopsis.


Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/genetics , Chromatin Assembly and Disassembly/genetics , Gene Expression Regulation, Developmental , Gene Expression Regulation, Plant , MicroRNAs/metabolism , Ovule/growth & development , Protein Serine-Threonine Kinases/metabolism , Receptors, Cell Surface/metabolism , Signal Transduction , Arabidopsis/growth & development , Arabidopsis Proteins/genetics , MicroRNAs/genetics , Models, Biological , Mutation/genetics , Protein Serine-Threonine Kinases/genetics , Receptors, Cell Surface/genetics , Time Factors , Transcription, Genetic
16.
Respir Res ; 25(1): 119, 2024 Mar 08.
Article in English | MEDLINE | ID: mdl-38459541

ABSTRACT

BACKGROUND: The pattern recognition receptor Dectin-1 was initially discovered to play a pivotal role in mediating pulmonary antifungal immunity and promoting neutrophil-driven inflammation. Recent studies have revealed that Dectin-1 is overexpressed in asthma, but the specific mechanism remains elusive. Additionally, Dectin-1 has been implicated in promoting pyroptosis, a hallmark of severe asthma airway inflammation. Nevertheless, the involvement of the non-classical pyroptosis signal caspase-11/4 and its upstream regulatory mechanisms in asthma has not been completely explored. METHODS: House dust mite (HDM)-induced mice was treated with Dectin-1 agonist Curdlan, Dectin-1 inhibitor Laminarin, and caspase-11 inhibitor wedelolactone separately. Subsequently, inflammatory cells in bronchoalveolar lavage fluid (BALF) were analyzed. Western blotting was performed to measure the protein expression of caspase-11 and gasdermin D (GSDMD). Cell pyroptosis and the expression of chemokine were detected in vitro. The correlation between Dectin-1 expression, pyroptosis factors and neutrophils in the induced sputum of asthma patients was analyzed. RESULTS: Curdlan appeared to exacerbate neutrophil airway inflammation in asthmatic mice, whereas wedelolactone effectively alleviated airway inflammation aggravated by Curdlan. Moreover, Curdlan enhanced the release of caspase-11 activation fragments and N-terminal fragments of gasdermin D (GSDMD-N) stimulated by HDM both in vivo or in vitro. In mouse alveolar macrophages (MH-S cells), Curdlan/HDM stimulation resulted in vacuolar degeneration and elevated lactate dehydrogenase (LDH) release. In addition, there was an upregulation of neutrophil chemokines CXCL1, CXCL3, CXCL5 and their receptor CXCR2, which was suppressed by wedelolactone. In asthma patients, a positive correlation was observed between the expression of Dectin-1 on macrophages and caspase-4 (the human homology of caspase-11), and the proportion of neutrophils in induced sputum. CONCLUSION: Dectin-1 activation in asthma induced caspase-11/4 mediated macrophage pyroptosis, which subsequently stimulated the secretion of chemokines, leading to the exacerbation of airway neutrophil inflammation.


Subject(s)
Asthma , Lectins, C-Type , Neutrophils , Animals , Humans , Mice , Asthma/metabolism , Caspases/metabolism , Chemokines/metabolism , Gasdermins , Inflammation/metabolism , Lung/metabolism , Macrophages/metabolism , Neutrophils/metabolism , Pyroglyphidae , Pyroptosis
17.
Exp Eye Res ; 242: 109870, 2024 May.
Article in English | MEDLINE | ID: mdl-38514023

ABSTRACT

Retinal neovascularization (RNV) is a pathological process that primarily occurs in diabetic retinopathy, retinopathy of prematurity, and retinal vein occlusion. It is a common yet debilitating clinical condition that culminates in blindness. Urgent efforts are required to explore more efficient and less limiting therapeutic strategies. Key RNA-binding proteins (RBPs), crucial for post-transcriptional regulation of gene expression by binding to RNAs, are closely correlated with RNV development. RBP-RNA interactions are altered during RNV. Here, we briefly review the characteristics and functions of RBPs, and the mechanism of RNV. Then, we present insights into the role of the regulatory network of RBPs in RNV. HuR, eIF4E, LIN28B, SRSF1, METTL3, YTHDF1, Gal-1, HIWI1, and ZFR accelerate RNV progression, whereas YTHDF2 and hnRNPA2B1 hinder it. The mechanisms elucidated in this review provide a reference to guide the design of therapeutic strategies to reverse abnormal processes.


Subject(s)
RNA-Binding Proteins , Retinal Neovascularization , Humans , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Retinal Neovascularization/metabolism , Retinal Neovascularization/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Gene Expression Regulation/physiology , Animals
18.
PLoS Biol ; 19(2): e3001099, 2021 02.
Article in English | MEDLINE | ID: mdl-33556049

ABSTRACT

In plants, conserved microRNAs (miRNAs) tend to be encoded by gene families with multiple members. Two recent studies interrogated the functions of the 5-member MIR172 family in Arabidopsis and revealed complexities and intricacies of gene regulatory networks underlying floral transition.


Subject(s)
Arabidopsis Proteins , Arabidopsis , MicroRNAs , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Family , Flowers/genetics , Flowers/metabolism , Gene Expression Regulation, Plant , Homeodomain Proteins/metabolism , Humans , MicroRNAs/genetics , N-Acetylglucosaminyltransferases , Plant Development/genetics
20.
Article in English | MEDLINE | ID: mdl-38240641

ABSTRACT

A Gram-stain-negative, catalase-positive and oxidase-positive, nonmotile, aerobic, light yellow, spherical-shaped bacterial strain with no flagella, designated strain YIM 152171T, was isolated from sediment of the South China Sea. Colonies were smooth and convex, light yellow and circular, and 1.0-1.5×1.0-1.5 µm in cell diameter after 7 days of incubation at 28°C on YIM38 media supplemented with sea salt. Colonies could grow at 20-45°C (optimum 28-35°C) and pH 6.0-11.0 (optimum, pH 7.0-9.0), and they could proliferate in the salinity range of 0-6.0 % (w/v) NaCl. The major cellular fatty acids were summed feature 8 (C18 : 1 ω7c/C18 : 1 ω6c), C18 : 1 ω7c 11-methyl, C16 : 0, C16 : 1 ω11c, C16 : 1 ω5c, C17 : 1 ω6c and C18 : 1 ω5c. The respiratory quinone was ubiquinone 10, and the polar lipid profile included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol mannoside, one unidentified phospholipid and one unidentified aminolipid. Phylogenetic analyses based on the 16S rRNA gene sequences placed strain YIM 152171T within the order Rhodospirillales in a distinct lineage that also included the genus Geminicoccus. The 16S rRNA gene sequence similarities of YIM 152171T to those of Arboricoccus pini, Geminicoccus roseus and Constrictibacter antarcticus were 92.17, 89.25 and 88.91 %, respectively. The assembled draft genome of strain YIM 152171T had 136 contigs with an N50 value of 134704 nt, a total length of 3 001 346 bp and a G+C content of 70.27 mol%. The phylogenetic, phenotypic and chemotaxonomic data showed that strain YIM 152171T (=MCCC 1K08488T=KCTC 92884T) represents a type of novel species and genus for which we propose the name Marinimicrococcus gen. nov., sp. nov.


Subject(s)
Fatty Acids , Rhodospirillales , Fatty Acids/chemistry , Phylogeny , RNA, Ribosomal, 16S/genetics , Bacterial Typing Techniques , Base Composition , DNA, Bacterial/genetics , Sequence Analysis, DNA , Geologic Sediments/microbiology , Phospholipids/chemistry , China
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