New research finds that disruptions in RNA communication, both within and outside the organism, can shorten the lifespan of Caenorhabditis elegans, providing new insights into the aging process and gene regulation.
Research on the roundworm species C. elegans shows that disruptions in the transfer of RNA between cells across different tissues can lead to shortened lifespan.
Cells in different tissues interact by sharing RNA molecules. A study conducted by scientists from the State University of Campinas (UNICAMP) in Brazil, using the roundworm Classified Caenorhabditis elegans found that disruptions in this method of communication can lead to a reduction in the organism’s lifespan. The study was recently published in the journal Gen. The results contribute to a better understanding of the aging process and related diseases.
“Previous research has shown that some types of RNA can be transferred from cell to cell, through communication between tissues, as occurs with proteins and metabolites, for example. It is a signaling mechanism between adjacent organs or cells. It is part of RNA.” [of the physiopathology] said Marcelo Mori, article author and professor at the Institute of Biology (IB-UNICAMP). “What wasn’t clear and we’ve now proven it is that changes in the patterns of ‘talk’ between RNA molecules can influence aging.”
The research was conducted at UNICAMP’s Obesity and Comorbidities Research Center (OCRC), one of the Research, Innovation and Dissemination Centers (RIDCs) funded by FAPESP. It is also funded by a project for which Mori is the principal investigator.
“These communication mechanisms must be finely tuned to give the organism an appropriate lifespan. In the study, we found that if any tissue increases its ability to absorb certain types of RNA from the extracellular environment, it ends up “This affects the lifespan of the organism.” organism.”
He added that researchers have proven that decreased lifespan is not only caused by disrupted RNA-based communication between tissues within the same organism, but also due to an increased ability to absorb RNA from the environment – bacteria found in microorganisms, for example. As they explain in the article, “Our data support the idea that systemic RNA signaling must be tightly regulated, and that an imbalance in this process leads to reduced lifespan. We call this phenomenon systemic intracellular/extracellular RNA dysregulation.” ).
break rules
Murray explained that the decision to investigate the mechanisms of RNA transfer between cells was inspired by the discovery of RNA interference, for which American scientists Andrew Fire and Craig Mello won the Nobel Prize in Physiology and Medicine in 2006. They injected double-stranded acid. RNA C. elegans To “silence” genes with great precision. “They found that the silencing mechanism affected genes in other tissues as well as that tissue, and it was passed on to the next generation,” he said.
The discovery of RNA interference has clarified the mechanisms behind RNA transfer between cells within an organism and between the organism and the environment. It also links the central doctrine to molecular biology. Until then, the information contained in the genetic code was thought to flow only from… DNA to RNA, and from there to proteins, but Fire and Craig’s research revealed that double-stranded RNA can block this flow. Messenger RNA is destroyed by RNA interference, which silences certain genes without changing the DNA sequence, suggesting that RNA can also perform regulatory functions in the genome. Although the human genome contains about 30,000 genes, only a few are used in each cell to synthesize proteins. Most of them play a regulatory role, influencing the expression of other genes.
Balance is everything
“We want to understand how this process can disrupt important physiological functions associated with aging C. elegansTransfer of RNA between cells involves what is known as an RNA interference defective (SID) gene. [responsible for different stages in RNA absorption and export]. We observed that the expression patterns of genes associated with these pathways in certain tissues changed with age. Messenger RNA encoding the SID-1 protein [fundamental to cellular uptake of RNA]“For example, it is increasing in some networks and decreasing in others,” Morey said.
To learn more about the role of RNA in tissue signaling, the researchers conducted experiments in which they manipulated the expression of the SID-1 protein in specific tissue lines. C. elegansSuch as nerve, intestinal and muscle cells, so that their function can be changed.
“We found that mutants lacking functional SID-1 were as healthy as wild-type worms, while overexpression of SID-1 in the gut, muscle, or neurons reduced the lifespan of individual worms. We also found that decreasing lifespan was also associated with this.” with overexpression of SID-1 in the intestine, muscle, or nerve cells. In the expression of other proteins in the RNA transport pathway, such as SID-2 and SID-5.
Dysregulation may underlie RNA distribution to tissues. “To disrupt RNA distribution in the worms, we increased SID-1 expression in certain tissues [gut, muscles, and neurons] It was found that directing it to certain organs caused a decrease in lifespan.
“We also show that defects in this transfer RNA lead to loss of function of the pathway that produces microRNAs.” [small pieces of non-coding RNA with a regulatory function]. It is as if more and more RNA is transferred to these tissues creating a kind of competition in which microRNA production is at a disadvantage. Previous studies have shown that loss of function in microRNA production leads to decreased lifespan.
The UNICAMP group also investigates exogenous RNA transfer (between the external environment and the organism). As in previous experiments, decreased lifespan was associated with overexpression of SID-2, which mediates uptake of RNA from the gut, and overproduction of RNA by bacteria that feed on the worms and end up in gut microorganisms.
“We think the worms may be using exogenous RNA to monitor microorganisms in the environment, but negative effects may occur when their tissues absorb excessive amounts,” Morey said. “When we forced the bacteria in the laboratory to express more dsRNA, the lifespan of the worms decreased. Excessive RNA transfer disrupts homeostasis and endogenous RNA production, which accelerates the aging process.”
Reference: “Tissue-specific overexpression of systemic RNA interference components limits the lifespan of C. elegans” by Henrique Camara, Mehmet Dinçer Inan, Karls A. Vergani-Junior, Silas Pinto, Thiago L. Knittel, Willian G. Salgueiro, Guilherme Tonon- da Silva, Juliana Ramírez, Diogo de Moraes, Dessie L. Braga, Evandro A. D’Souza and Marcelo A. Mori, 18 November 2023, Gen.
doi: 10.1016/j.gene.2023.148014
This study was funded by the Sao Paulo Research Foundation.
2024-02-21 10:37:31
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