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Researchers at Indiana University Bloomington have uncovered previously hidden steps of a gene silencing process used to combat viruses and other would-be genome invaders.
The new findings, published in Genes & Development, report the work of a team led by first-author, Dr. Feng Wang in the laboratory of Distinguished Professor of Biology and Molecular and Cellular Biochemistry, Craig Pikaard. The study reveals how a member of an important protein family, ARGONAUTE 4 (AGO4), binds, cuts and retains snippets of ribonucleic acid (RNA) molecules that guide the chemical inactivation of genes with matching sequences.
Gene silencing mediated by RNA molecules is known as RNA interference, or RNAi, and occurs in diverse organisms that include animals, insects, plants, and fungi. There are several different types of RNAi, but all share common features. All begin with RNA polymerase proteins reading the genetic information stored in DNA and copying it into RNA, a process known as transcription.
In all RNAi pathways, double-stranded RNAs (dsRNAs) are synthesized, with the two strands paired like a DNA double-helix. These dsRNAs are cut by Dicer proteins into shorter dsRNAs whose individual strands can range from ~21-35 nucleotides (the individual units of RNA polymers) depending on the species and RNAi pathway. The diced dsRNAs are then loaded into an Argonaute family protein. Only one strand, known as the guide strand, is destined to remain stably associated with the AGO protein.
The other strand, known as the passenger strand, is released and degraded. The AGO protein then uses the guide strand to find RNA targets to which the guide strand can pair, leading to gene silencing by different means. In one scenario, used to inactivate RNAs that encode…
2023-02-06 15:53:04 Argonaute protein slicing, retention of RNA fragments plays role in chemical modification of DNA for gene silencing
Source from phys.org
Recent research on Argonaute proteins has uncovered a novel role for their slicing ability in chemical modification of DNA for gene silencing. Argonaute proteins are a type of enzyme that binds to small single-stranded RNAs (ss RNAs). They act to “slice” the RNAs, breaking them into fragments. The fragments are known as RNA-induced silencing complexes (RISCs) and have been an essential component in the study of RNA interference (RNAi), a process that regulates gene expression.
Until recently, it was thought that Argonaute proteins acted solely on ss RNAs. A recent study has revealed, however, that the retention of RNA fragments after slicing by Argonaute proteins has an unexpected role in DNA modification. When Argonaute slicing takes place, the protein retains two smaller ss RNA fragments that target and bind to a specific site on a DNA molecule. This binding is then followed by the binding of a methyltransferase enzyme that chemically modifies the DNA, inactivating the gene. The Argonaute protein acts as a “landing-pad” for the methyltransferase and significantly enhances the efficiency of gene silencing.
The identification of the role of Argonaute-retained RNA fragments in chemical modification of DNA has expanded our understanding of gene silencing processes. It has opened the door to new ways of modulating gene expression and creating treatments for genetic diseases associated with epigenetic changes caused by DNA methylation.
Overall, this research has demonstrated the importance of Argonaute proteins in gene silencing. It has revealed their ability to act as a “landing-pad” for methyltransferase enzymes, which are essential in silencing genes. Further studies are necessary to elucidate the exact mechanism by which Argonaute and retained RNA fragments coordinately mediate gene silencing.