scholarly journals Inheritance of associative memories in C. elegans nematodes

2020 ◽  
Author(s):  
Noa Deshe ◽  
Yifat Eliezer ◽  
Lihi Hoch ◽  
Eyal Itskovits ◽  
Shachaf Ben-Ezra ◽  
...  
Keyword(s):  
Associative Memory ◽  
Stress Responses ◽  
Rna Binding ◽  
Associative Memories ◽  
C Elegans ◽  
Fitness Advantage ◽  
Neuropeptide Secretion ◽  
Two Generations ◽  
Chemosensory Neuron ◽  
Systemic Stress

SummaryThe notion that associative memories may be transmitted across generations is intriguing, yet controversial. Here, we trained C. elegans nematodes to associate an odorant with stressful starvation conditions, and surprisingly, this associative memory was evident two generations down of the trained animals. The inherited memory endowed the progeny with a fitness advantage, as memory reactivation induced rapid protective stress responses that allowed the animals to prepare in advance for an impending adversity. Sperm, but not oocytes, transmitted the associative memory, and the inheritance required H3K9 and H3K36 methylations, the small RNA-binding Argonaute NRDE-3, and intact neuropeptide secretion. Remarkably, activation of a single chemosensory neuron sufficed to induce a serotonin-mediated systemic stress response in both the parental trained generation and in its progeny. These findings challenge long-held concepts by establishing that associative memories may indeed be transferred across generations.

scholarly journals Nervous system-wide profiling of presynaptic mRNAs reveals regulators of associative memory

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Rachel N. Arey ◽  
Rachel Kaletsky ◽  
Coleen T. Murphy
Keyword(s):  
Nervous System ◽  
Associative Memory ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Fluorescent Proteins ◽  
Differential Expression Analysis ◽  
High Sensitivity ◽  
Synaptic Function ◽  
Sequencing Analysis ◽  
C Elegans

AbstractPresynaptic protein synthesis is important in the adult central nervous system; however, the nervous system-wide set of mRNAs localized to presynaptic areas has yet to be identified in any organism. Here we differentially labeled somatic and synaptic compartments in adult C. elegans with fluorescent proteins, and isolated synaptic and somatic regions from the same population of animals. We used this technique to determine the nervous system-wide presynaptic transcriptome by deep sequencing. Analysis of the synaptic transcriptome reveals that synaptic transcripts are predicted to have specialized functions in neurons. Differential expression analysis identified 542 genes enriched in synaptic regions relative to somatic regions, with synaptic functions conserved in higher organisms. We find that mRNAs for pumilio RNA-binding proteins are abundant in synaptic regions, which we confirmed through high-sensitivity in situ hybridization. Presynaptic PUMILIOs regulate associative memory. Our approach enables the identification of new mechanisms that regulate synaptic function and behavior.

scholarly journals Distinct phases within large RNP granules of C. elegans oocytes are associated with differential stress responses of RNA binding proteins

2021 ◽  
Author(s):  
Brooklynne Watkins ◽  
Mohamed T. Elaswad ◽  
Chloe Pestrue ◽  
Katherine Sharp ◽  
Elizabeth Breton ◽  
...  
Keyword(s):  
Stress Responses ◽  
Binding Proteins ◽  
Rna Binding ◽  
Intermediate Phase ◽  
Rna Binding Proteins ◽  
Oocyte Quality ◽  
C Elegans ◽  
Disease States ◽  
Germ Granules ◽  
Rnp Granules

One emerging paradigm of cellular organization of RNA and RNA binding proteins is the formation of membraneless organelles (MLOs). Examples of MLOs include several types of RNP (ribonucleoprotein) granules that form via phase separation. Proper regulation of the phase transitions of RNA binding proteins is critical as dysregulation can lead to disease states. Germ granules are small RNP granules conserved across metazoa. In C. elegans, when oogenesis undergoes an extended meiotic arrest, germ granules assemble into much larger, more complex RNP granules whose hypothesized function is to regulate RNA metabolism and maintain oocyte quality. As a step towards gaining insight into the function of RNP granules, in this report we characterize distinct phases for four RNA binding proteins in arrested oocytes. We find that PGL-1 is dynamic and has liquid-like properties, while MEG-3 has gel-like properties, both similar to their properties in small germ granules of embryos. We also show that MEX-3 exhibits gel-like properties in many regards but is more dynamic than MEG-3. We find CGH-1 is dynamic but does not consistently behave liquid-like, and may be an intermediate phase within RNP granules. We also show that the distinct phases of the RNA binding proteins are associated with differential responses to stress.

scholarly journals Novel Insights into YB-1 Signaling and Cell Death Decisions

Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3306
Author(s):  
Aneri Shah ◽  
Jonathan A. Lindquist ◽  
Lars Rosendahl ◽  
Ingo Schmitz ◽  
Peter R. Mertens
Keyword(s):  
Stress Responses ◽  
Rna Splicing ◽  
Cell Cycle Progression ◽  
Rna Binding ◽  
Inflammatory Responses ◽  
Rna Binding Proteins ◽  
Inflammatory Diseases ◽  
Therapeutic Option ◽  
Tumor Therapy ◽  
Inflammatory Microenvironment

YB-1 belongs to the evolutionarily conserved cold-shock domain protein family of RNA binding proteins. YB-1 is a well-known transcriptional and translational regulator, involved in cell cycle progression, DNA damage repair, RNA splicing, and stress responses. Cell stress occurs in many forms, e.g., radiation, hyperthermia, lipopolysaccharide (LPS) produced by bacteria, and interferons released in response to viral infection. Binding of the latter factors to their receptors induces kinase activation, which results in the phosphorylation of YB-1. These pathways also activate the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a well-known transcription factor. NF-κB is upregulated following cellular stress and orchestrates inflammatory responses, cell proliferation, and differentiation. Inflammation and cancer are known to share common mechanisms, such as the recruitment of infiltrating macrophages and development of an inflammatory microenvironment. Several recent papers elaborate the role of YB-1 in activating NF-κB and signaling cell survival. Depleting YB-1 may tip the balance from survival to enhanced apoptosis. Therefore, strategies that target YB-1 might be a viable therapeutic option to treat inflammatory diseases and improve tumor therapy.

scholarly journals Genome-wide Identification and Expression Analysis of the YTH Domain-containing RNA-binding Protein Family in Citrus Sinensis

2019 ◽  
Vol 144 (2) ◽  
pp. 79-91 ◽  
Author(s):  
Zhigang Ouyang ◽  
Huihui Duan ◽  
Lanfang Mi ◽  
Wei Hu ◽  
Jianmei Chen ◽  
...  
Keyword(s):  
Stress Responses ◽  
Messenger Rna ◽  
Citrus Sinensis ◽  
Rna Binding ◽  
Developmental Stages ◽  
Rna Binding Proteins ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Genome Wide ◽  
Yth Domain

In eukaryotic systems, messenger RNA regulations, including splicing, 3′-end formation, editing, localization, and translation, are achieved by different RNA-binding proteins and noncoding RNAs. The YTH domain is a newly identified RNA-binding domain that was identified by comparing its sequence with that of splicing factor YT521-B. Previous study showed that the YTH gene plays an important role in plant resistance to abiotic and biotic stress. In this study, 211 YTH genes were identified in 26 species that represent four major plant lineages. Phylogenetic analysis revealed that these genes could be divided into eight subgroups. All of the YTH genes contain a YT521 domain and have different structures. Ten YTH genes were identified in navel orange (Citrus sinensis). The expression profiles of these CitYTH genes were analyzed in different tissues and at different fruit developmental stages, and CitYTH genes displayed distinct expression patterns under heat, cold, salt, and drought stress. Furthermore, expression of the CitYTH genes in response to exogenous hormones was measured. Nuclear localization was also confirmed for five of the proteins encoded by these genes after transient expression in Nicotiana benthamiana cells. This study provides valuable information on the role of CitYTHs in the signaling pathways involved in environmental stress responses in Citrus.

scholarly journals Eukaryotic initiation factor EIF-3.G augments mRNA translation efficiency to regulate neuronal activity

2021 ◽  
Author(s):  
Stephen M Blazie ◽  
Seika Takayanagi-Kiya ◽  
Katherine A McCulloch ◽  
Yishi Jin
Keyword(s):  
Rna Binding ◽  
Mrna Translation ◽  
Initiation Factor ◽  
Translation Efficiency ◽  
Dependent Manner ◽  
Control Activity ◽  
C Elegans ◽  
Protein Levels ◽  
Neuronal Protein

AbstractThe translation initiation complex eIF3 imparts specialized functions to regulate protein expression. However, understanding of eIF3 activities in neurons remains limited despite widespread dysregulation of eIF3 subunits in neurological disorders. Here, we report a selective role of theC. elegansRNA-binding subunit EIF-3.G in shaping the neuronal protein landscape. We identify a missense mutation in the conserved Zinc-Finger (ZF) of EIF-3.G that acts in a gain-of-function manner to dampen neuronal hyperexcitation. Using neuron type-specific seCLIP, we systematically mapped EIF-3.G-mRNA interactions and identified EIF-3.G occupancy on GC-rich 5′UTRs of a select set of mRNAs enriched in activity-dependent functions. We demonstrate that the ZF mutation in EIF-3.G alters translation in a 5′UTR dependent manner. Our study reveals anin vivomechanism for eIF3 in governing neuronal protein levels to control activity states and offers insights into how eIF3 dysregulation contributes to neuronal disorders.

scholarly journals An intestinally secreted host factor promotes microsporidia invasion of C. elegans

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Hala Tamim El Jarkass ◽  
Calvin Mok ◽  
Michael R Schertzberg ◽  
Andrew G Fraser ◽  
Emily R Troemel ◽  
...  
Keyword(s):  
Bacterial Pathogen ◽  
Oral Route ◽  
Intestinal Lumen ◽  
Wild Type ◽  
Parasite Invasion ◽  
Competitive Fitness ◽  
Obligate Intracellular ◽  
C Elegans ◽  
Fitness Advantage ◽  
Trade Offs

Microsporidia are ubiquitous obligate intracellular pathogens of animals. These parasites often infect hosts through an oral route, but little is known about the function of host intestinal proteins that facilitate microsporidia invasion. To identify such factors necessary for infection by Nematocida parisii, a natural microsporidian pathogen of Caenorhabditis elegans, we performed a forward genetic screen to identify mutant animals that have a Fitness Advantage with Nematocida (Fawn). We isolated four fawn mutants that are resistant to Nematocida infection and contain mutations in T14E8.4, which we renamed aaim-1 (Antibacterial and Aids invasion by Microsporidia). Expression of AAIM-1 in the intestine of aaim-1 animals restores N. parisii infectivity and this rescue of infectivity is dependent upon AAIM-1 secretion. N. parisii spores in aaim-1 animals are improperly oriented in the intestinal lumen, leading to reduced levels of parasite invasion. Conversely, aaim-1 mutants display both increased colonization and susceptibility to the bacterial pathogen Pseudomonas aeruginosa and overexpression of AAIM-1 reduces P. aeruginosa colonization. Competitive fitness assays show that aaim-1 mutants are favoured in the presence of N. parisii but disadvantaged on P. aeruginosa compared to wild type animals. Together, this work demonstrates how microsporidia exploits a secreted protein to promote host invasion. Our results also suggest evolutionary trade-offs may exist to optimizing host defense against multiple classes of pathogens.

scholarly journals Functions of PPR Proteins in Plant Growth and Development

2021 ◽  
Vol 22 (20) ◽  
pp. 11274
Author(s):  
Xiulan Li ◽  
Mengdi Sun ◽  
Shijuan Liu ◽  
Qian Teng ◽  
Shihui Li ◽  
...  
Keyword(s):  
Plant Growth ◽  
Stress Responses ◽  
Rna Processing ◽  
Growth And Development ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Plant Mitochondria ◽  
Research Progress ◽  
Plant Growth And Development ◽  
Ppr Proteins

Pentatricopeptide repeat (PPR) proteins form a large protein family in land plants, with hundreds of different members in angiosperms. In the last decade, a number of studies have shown that PPR proteins are sequence-specific RNA-binding proteins involved in multiple aspects of plant organellar RNA processing, and perform numerous functions in plants throughout their life cycle. Recently, computational and structural studies have provided new insights into the working mechanisms of PPR proteins in RNA recognition and cytidine deamination. In this review, we summarized the research progress on the functions of PPR proteins in plant growth and development, with a particular focus on their effects on cytoplasmic male sterility, stress responses, and seed development. We also documented the molecular mechanisms of PPR proteins in mediating RNA processing in plant mitochondria and chloroplasts.

scholarly journals rab-27 acts in an intestinal pathway to inhibit axon regeneration in C. elegans

PLoS Genetics ◽  
2021 ◽  
Vol 17 (11) ◽  
pp. e1009877
Author(s):  
Alexander T. Lin-Moore ◽  
Motunrayo J. Oyeyemi ◽  
Marc Hammarlund
Keyword(s):  
Motor Neurons ◽  
Axon Regeneration ◽  
Rab Gtpase ◽  
Long Distance ◽  
Extrinsic Factors ◽  
C Elegans ◽  
Cellular Environment ◽  
Neuropeptide Secretion ◽  
Neuronal Tissues ◽  
Nervous System Function

Injured axons must regenerate to restore nervous system function, and regeneration is regulated in part by external factors from non-neuronal tissues. Many of these extrinsic factors act in the immediate cellular environment of the axon to promote or restrict regeneration, but the existence of long-distance signals regulating axon regeneration has not been clear. Here we show that the Rab GTPase rab-27 inhibits regeneration of GABAergic motor neurons in C. elegans through activity in the intestine. Re-expression of RAB-27, but not the closely related RAB-3, in the intestine of rab-27 mutant animals is sufficient to rescue normal regeneration. Several additional components of an intestinal neuropeptide secretion pathway also inhibit axon regeneration, including NPDC1/cab-1, SNAP25/aex-4, KPC3/aex-5, and the neuropeptide NLP-40, and re-expression of these genes in the intestine of mutant animals is sufficient to restore normal regeneration success. Additionally, NPDC1/cab-1 and SNAP25/aex-4 genetically interact with rab-27 in the context of axon regeneration inhibition. Together these data indicate that RAB-27-dependent neuropeptide secretion from the intestine inhibits axon regeneration, and point to distal tissues as potent extrinsic regulators of regeneration.

scholarly journals Investigating the Roles of RNA Binding Protein Combinations in Neuronal Function and Organismal Behavior

2019 ◽  
Vol 4 (Spring 2019) ◽  
Author(s):  
Alexa Vandenburg
Keyword(s):  
Binding Sites ◽  
Neuronal Development ◽  
Rna Binding ◽  
Rna Binding Proteins ◽  
Binding Protein ◽  
Rna Binding Protein ◽  
Wild Type ◽  
C Elegans ◽  
Neuronal Gene ◽  
Touch Response

The Norris lab recently identified two RNA binding proteins required for proper neuron-specific splicing. The lab conducted touch- response behavioral assays to assess the function of these proteins in touch-sensing neurons. After isolating C. elegans worms with specific phenotypes, the lab used automated computer tracking and video analysis to record the worms’ behavior. The behavior of mutant worms differed from that of wild-type worms. The Norris lab also discovered two possible RNA binding protein sites in SAD-1, a neuronal gene implicated in the neuronal development of C. elegans1. These two binding sites may control the splicing of SAD-1. The lab transferred mutated DNA into the genome of wild-type worms by injecting a mutated plasmid. The newly transformed worms fluoresced green, indicating that the two binding sites control SAD-1 splicing.

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