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1.
Cell ; 177(7): 1814-1826.e15, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31178120

RESUMO

It is unknown whether the activity of the nervous system can be inherited. In Caenorhabditis elegans nematodes, parental responses can transmit heritable small RNAs that regulate gene expression transgenerationally. In this study, we show that a neuronal process can impact the next generations. Neurons-specific synthesis of RDE-4-dependent small RNAs regulates germline amplified endogenous small interfering RNAs (siRNAs) and germline gene expression for multiple generations. Further, the production of small RNAs in neurons controls the chemotaxis behavior of the progeny for at least three generations via the germline Argonaute HRDE-1. Among the targets of these small RNAs, we identified the conserved gene saeg-2, which is transgenerationally downregulated in the germline. Silencing of saeg-2 following neuronal small RNA biogenesis is required for chemotaxis under stress. Thus, we propose a small-RNA-based mechanism for communication of neuronal processes transgenerationally.


Assuntos
Comportamento Animal , Caenorhabditis elegans , Neurônios/metabolismo , RNA de Helmintos , Pequeno RNA não Traduzido , Animais , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Caenorhabditis elegans/citologia , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Neurônios/citologia , RNA de Helmintos/biossíntese , RNA de Helmintos/genética , Pequeno RNA não Traduzido/biossíntese , Pequeno RNA não Traduzido/genética
2.
Worm ; 3(4): e989798, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26430554

RESUMO

Caenorhabditis elegans (C. elegans) nematodes transmit small RNAs across generations, a process that enables transgenerational regulation of genes. In contrast to changes to the DNA sequence, transgenerational transmission of small RNA-mediated responses is reversible, and thus enables "soft" or "flexible" inheritance of acquired characteristics. Until very recently only introduction of foreign genetic material (viruses, transposons, transgenes) was shown to directly lead to inheritance of small RNAs. New discoveries however, demonstrate that starvation also triggers inheritance of endogenous small RNAs in C.elegans. Multiple generations of worms inherit starvation-responsive endogenous small RNAs, and starvation also results in heritable extension of the progeny's lifespan. In this Commentary paper we explore the intriguing possibility that large parts of the genome and many additional traits are similarly subjected to heritable small RNA-mediated regulation, and focus on the potential influence of transgenerational RNAi on the worm's physiology. While the universal relevance of this mechanism remains to be discovered, we will examine how the discoveries made in worms already challenge long held dogmas in genetics and evolution.

3.
Clin Transl Sci ; 7(2): 100-7, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24456567

RESUMO

The 61 CTSA Consortium sites are home to valuable programs and infrastructure supporting translational science and all are charged with ensuring that such investments translate quickly to improved clinical care. Catalog of Assets for Translational and Clinical Health Research (CATCHR) is the Consortium's effort to collect and make available information on programs and resources to maximize efficiency and facilitate collaborations. By capturing information on a broad range of assets supporting the entire clinical and translational research spectrum, CATCHR aims to provide the necessary infrastructure and processes to establish and maintain an open-access, searchable database of consortium resources to support multisite clinical and translational research studies. Data are collected using rigorous, defined methods, with the resulting information made visible through an integrated, searchable Web-based tool. Additional easy-to-use Web tools assist resource owners in validating and updating resource information over time. In this paper, we discuss the design and scope of the project, data collection methods, current results, and future plans for development and sustainability. With increasing pressure on research programs to avoid redundancy, CATCHR aims to make available information on programs and core facilities to maximize efficient use of resources.


Assuntos
Catálogos como Assunto , Comportamento Cooperativo , Pesquisa sobre Serviços de Saúde , Pesquisa Translacional Biomédica , Coleta de Dados , Ensaios de Triagem em Larga Escala , Humanos , Internet , Reprodutibilidade dos Testes , Interface Usuário-Computador
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