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Heterochromatin is a tightly packed form of DNA or condensed DNA, which comes in multiple varieties. These varieties lie on a continuum between the two extremes of constitutive heterochromatin and facultative heterochromatin. Both play a role in the expression of genes. Because it is tightly packed, it was thought to be inaccessible to polymerases and therefore not transcribed; however, according to Volpe et al. (2002), and many other papers since, much of this DNA is in fact transcribed, but it is continuously turned over via RNA-induced transcriptional silencing (RITS). Recent studies with electron microscopy and OsO4 staining reveal that the dense packing is not due to the chromatin.
Molecular genetics is a branch of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the structure and/or function of genes in an organism's genome using genetic screens.
Small interfering RNA (siRNA), sometimes known as short interfering RNA or silencing RNA, is a class of double-stranded RNA at first non-coding RNA molecules, typically 20–24 base pairs in length, similar to miRNA, and operating within the RNA interference (RNAi) pathway. It interferes with the expression of specific genes with complementary nucleotide sequences by degrading mRNA after transcription, preventing translation. It was discovered in 1998, by Andrew Fire at Carnegie Institution for Science in Washington DC and Craig Mello at University of Massachusetts in Worcester.
Dicer, also known as endoribonuclease Dicer or helicase with RNase motif, is an enzyme that in humans is encoded by the DICER1 gene. Being part of the RNase III family, Dicer cleaves double-stranded RNA (dsRNA) and pre-microRNA (pre-miRNA) into short double-stranded RNA fragments called small interfering RNA and microRNA, respectively. These fragments are approximately 20–25 base pairs long with a two-base overhang on the 3′-end. Dicer facilitates the activation of the RNA-induced silencing complex (RISC), which is essential for RNA interference. RISC has a catalytic component Argonaute, which is an endonuclease capable of degrading messenger RNA (mRNA).
A primary transcript is the single-stranded ribonucleic acid (RNA) product synthesized by transcription of DNA, and processed to yield various mature RNA products such as mRNAs, tRNAs, and rRNAs. The primary transcripts designated to be mRNAs are modified in preparation for translation. For example, a precursor mRNA (pre-mRNA) is a type of primary transcript that becomes a messenger RNA (mRNA) after processing.
The RNA-induced silencing complex, or RISC, is a multiprotein complex, specifically a ribonucleoprotein, which functions in gene silencing via a variety of pathways at the transcriptional and translational levels. Using single-stranded RNA (ssRNA) fragments, such as microRNA (miRNA), or double-stranded small interfering RNA (siRNA), the complex functions as a key tool in gene regulation. The single strand of RNA acts as a template for RISC to recognize complementary messenger RNA (mRNA) transcript. Once found, one of the proteins in RISC, Argonaute, activates and cleaves the mRNA. This process is called RNA interference (RNAi) and it is found in many eukaryotes; it is a key process in defense against viral infections, as it is triggered by the presence of double-stranded RNA (dsRNA).
Cell is a peer-reviewed scientific journal publishing research papers across a broad range of disciplines within the life sciences. Areas covered include molecular biology, cell biology, systems biology, stem cells, developmental biology, genetics and genomics, proteomics, cancer research, immunology, neuroscience, structural biology, microbiology, virology, physiology, biophysics, and computational biology. The journal was established in 1974 by Benjamin Lewin and is published twice monthly by Cell Press, an imprint of Elsevier.
Polycomb-group proteins are a family of protein complexes first discovered in fruit flies that can remodel chromatin such that epigenetic silencing of genes takes place. Polycomb-group proteins are well known for silencing Hox genes through modulation of chromatin structure during embryonic development in fruit flies. They derive their name from the fact that the first sign of a decrease in PcG function is often a homeotic transformation of posterior legs towards anterior legs, which have a characteristic comb-like set of bristles.
The Argonaute protein family, first discovered for its evolutionarily conserved stem cell function, plays a central role in RNA silencing processes as essential components of the RNA-induced silencing complex (RISC). RISC is responsible for the gene silencing phenomenon known as RNA interference (RNAi). Argonaute proteins bind different classes of small non-coding RNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs) and Piwi-interacting RNAs (piRNAs). Small RNAs guide Argonaute proteins to their specific targets through sequence complementarity, which then leads to mRNA cleavage, translation inhibition, and/or the initiation of mRNA decay.
Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA molecules expressed in animal cells. piRNAs form RNA-protein complexes through interactions with piwi-subfamily Argonaute proteins. These piRNA complexes are mostly involved in the epigenetic and post-transcriptional silencing of transposable elements and other spurious or repeat-derived transcripts, but can also be involved in the regulation of other genetic elements in germ line cells.
Piwi genes were identified as regulatory proteins responsible for stem cell and germ cell differentiation. Piwi is an abbreviation of P-elementInduced WImpy testis in Drosophila. Piwi proteins are highly conserved RNA-binding proteins and are present in both plants and animals. Piwi proteins belong to the Argonaute/Piwi family and have been classified as nuclear proteins. Studies on Drosophila have also indicated that Piwi proteins have no slicer activity conferred by the presence of the Piwi domain. In addition, Piwi associates with heterochromatin protein 1, an epigenetic modifier, and piRNA-complementary sequences. These are indications of the role Piwi plays in epigenetic regulation. Piwi proteins are also thought to control the biogenesis of piRNA as many Piwi-like proteins contain slicer activity which would allow Piwi proteins to process precursor piRNA into mature piRNA.
Sir David Charles Baulcombe is a British plant scientist and geneticist. As of 2017 he is a Royal Society Research Professor. From 2007 to 2020 he was Regius Professor of Botany in the Department of Plant Sciences at the University of Cambridge.
In molecular biology, a Tudor domain is a conserved protein structural domain originally identified in the Tudor protein encoded in Drosophila. The Tudor gene was found in a Drosophila screen for maternal factors that regulate embryonic development or fertility. Mutations here are lethal for offspring, inspiring the name Tudor, as a reference to the Tudor King Henry VIII and the several miscarriages experienced by his wives.
The Institute of Molecular Biotechnology (IMBA) is an independent biomedical research organisation founded by the Austrian Academy of Sciences in cooperation with the pharmaceutical company Boehringer Ingelheim. The institute employs around 250 people from over 40 countries, who perform basic research. IMBA is located at the Vienna BioCenter (VBC) and shares facilities and scientific training programs with the Gregor Mendel Institute of Molecular Plant Biology (GMI) of the Austrian Academy of Sciences and the Research Institute of Molecular Pathology (IMP), the basic research center of Boehringer Ingelheim.
RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by other names, including co-suppression, post-transcriptional gene silencing (PTGS), and quelling. The detailed study of each of these seemingly different processes elucidated that the identity of these phenomena were all actually RNAi. Andrew Fire and Craig C. Mello shared the 2006 Nobel Prize in Physiology or Medicine for their work on RNAi in the nematode worm Caenorhabditis elegans, which they published in 1998. Since the discovery of RNAi and its regulatory potentials, it has become evident that RNAi has immense potential in suppression of desired genes. RNAi is now known as precise, efficient, stable and better than antisense therapy for gene suppression. Antisense RNA produced intracellularly by an expression vector may be developed and find utility as novel therapeutic agents.
Ruth Lehmann is a developmental and cell biologist. She is the Director of the Whitehead Institute for Biomedical Research. She previously was affiliated with the New York University School of Medicine, where she was the Director of the Skirball Institute of Biomolecular Medicine, the Laura and Isaac Perlmutter Professor of Cell Biology, and the Chair of the Department of Cell Biology. Her research focuses on germ cells and embryogenesis.
Phillip D. Zamore is an American molecular biologist and biochemist who co-developed the first in vitro system for studying the mechanism of RNA interference (RNAi). He is the Gretchen Stone Cook Professor of Biomedical Sciences at University of Massachusetts Chan Medical School, Worcester, Massachusetts. Zamore is chair of the RNA Therapeutics Institute (RTI), established in 2009, and has been a Howard Hughes Medical Institute Investigator since 2008.
Julius Brennecke is a German molecular biologist and geneticist. He is a Senior Group Leader at the Institute of Molecular Biotechnology. (IMBA) of the Austrian Academy of Sciences in Vienna.
Richard William Carthew is a developmental biologist and quantitative biologist at Northwestern University. He is a professor of molecular biosciences and is the director of the NSF-Simons Center for Quantitative Biology.
Howard David Lipshitz is an American and Canadian biologist who does genetic research on the fruit fly, Drosophila.
References
- ↑ Pham, John W. (2006). Building the Drosophila RNA-induced silencing complex (Thesis). OCLC 124095747.
- 1 2 3 Caputo, Joseph (2018-07-26). "A Q&A with John Pham, the new Editor-in-Chief of Cell". crosstalk.cell.com. Retrieved 2019-07-08.
- 1 2 3 Parsons, David James (2019-06-20). "Elsevier and 500 Queer Scientists to hold NYC event for World Pride". Elsevier Connect. Retrieved 2019-07-08.
- 1 2 3 "Dr. John Pham appointed as new Editor-in-Chief of Cell". www.elsevier.com. Retrieved 2019-07-08.
- ↑ Pham, John W. (2006). Building the Drosophila RNA-induced silencing complex (Thesis). OCLC 124095747.
- ↑ "Reflections of a reluctant leader - with John Pham, editor of Cell". Listen Notes. Retrieved 2021-10-08.