Rna Interference Regulates Gene Expression

Studying various genome-related hypotheses, including their functions in regenerative organ growth, adaptive systems, population adaptation, and the connections between structure, function, and evolution of genomes.

The Mechanisms of gene regulation are used by a cell to determine whether to increse or decrease

Dr. Tina Henkin’s seminar “Flipping the switch: How cells use RNA to regulate genes expression”, was outlined by four general questions. The first question addressed in the seminar was “Why study Microbes?”. The next, “Why study bacterial gene regulation?”. The third question, “What are the basics of gene expression?”. Finally, “What’s special about riboswitches?”. Dr. Henkin addressed these questions throughout her seminar, which eventually led into to more specific questions of gene expression and predicted hypotheses of her model. However, to understand these more specific questions and predictions it is crucial to understand the first four questions outlined in the beginning of the seminar.

RNA interference takes advantage of an intermediate step between DNA and protein. DNA acts as a blueprint for the final protein by using messenger RNA (mRNA) . The mRNA is a messenger molecule between DNA and protein synthesis. There is a two steps process need to be completed in order to go from gene to protein. The first step in protein synthesis is transcription, it takes place in a cell’s nucleus, where the DNA template is used to make a single strand of mRNA. Then, the messenger RNA exits the nucleus and enters the cytoplasm. Now it serves as the template for making the protein. After that, with the help of several different molecules, a string of amino acids forms due to the order of the mRNA bases. This process is called translation

Sir2 and Hst1 have high sequence similarity (see figure 2), and in high copy numbers, they may partially compensate for one another; however, they do not function in place of one another under normal cellular conditions. The subtle differences between these two proteins therefore must determine which cofactors they interact with, and therefore what role in silencing or repression they play. In order to study this, the Vershon lab created a series of “chimera” proteins which swapped similar regions of Hst1 into Sir2 and vice versa in order to study which regions of the proteins were responsible for cofactor interactions (Mead et al, 2007). Through this study, they determined that the N-terminus of Sir2 is responsible for interaction with Sir3 and Sir4. They also determined the region of Hst1 required for interaction with Sum1 and Rfm1; this region is highly conserved, so they then created a series of individual amino acid swaps within that region to determine which amino acids were responsible for the cofactor interactions. They then

The central dogma of molecular biology states that DNA passes genetic information to RNA through a process called transcription and RNA uses the genetic information to code for proteins through a process called translation. Effects of cell differentiation can be seen at many points throughout this process, including in the proteins produced following translation. Differences in these proteins produced can be analyzed by looking at the enzymatic activity of the proteins. Analyzing enzymatic activity in proteins can be helpful in many situations, such as when analyzing how to fight certain diseases scientists could analyze the proteins that the diseased cells produce and then use that information to make medicines that can destroy those proteins to prevent the diseased

As cells differentiate into specialized cell types they undergo re-organization and many structural changes which affects gene expression patterns and cell functions. Chromatin interactions have important roles in gene regulation.

The innate immune response uses so-called pattern-recognition receptors (PRRs), which recognize specific molecular patterns that are inevitable for the survival of a pathogen (Licht and Jantsch). This response allows for the organisms to combat a pathogen, while not causing harm to the organism. However, one of the most intriguing questions is how PRRs distinguish “self” from “nonself.” Here, A-to-I editing plays a key role, since A-to-I editing represses nucleic acid–induced inflammation signaling and discriminates self from nonself dsRNA (Licht and Jantsch). The dsRNA is a virus in which the genetic material on its core is a double stranded RNA. The dsRNA viruses replicate in the cytoplasm, and their replication is monocistronic, ergo it is a type of messenger RNA that can only encode one polypeptide per RNA molecule. The RNA editing enzyme ADAR1 has recently emerged as a key regulator that prevents innate immune pathway activation from inducing interferon in response to double-stranded RNA structures within endogenous RNAs. Interferons, which are generally secreted from the cell that detects the foreign RNA, are soluble alarm signals that set up a latent anti-viral state in neighboring cells by inducing the expression of scores of interferon stimulated genes. Viral sequences are edited differently from cellular RNAs, which can lead to increased

DNA is associated with specific proteins called histones which compact and package the chromosomes into the nucleus. The resulting DNA-protein complex is called chromatin. The packaging of DNA into chromatin can impact the ability of the numerous proteins and enzymes to gain access to specific genes before activating their transcription. The chromatin structure can be altered, either being loosened to facilitate gene expression or tightened to limit gene expression. These alternations are largely mediated by reversible modifications of the histones through a dynamic, tightly regulated process called chromatin remodeling. Chromatin remodeling mediates differential gene expression and is therefore crucial for development, cell type-specific gene

The siRNA molecule is the product of the RNA interference (RNAi) pathway. The starting molecule in the pathway is a long “triggering” double stranded RNA (dsRNA). The dsRNA is formed from either an RNAi molecule inserted into the cell or a siRNA which complexes with a specific strand of messenger RNA

Once dsRNA is injected it binds to Dicer, an endonuclease protein that cuts RNA into short segments of 21 nucleotides long that are siRNA or micro RNAs. The short dsRNA binds to an argonaute protein and a guide strand is selected. The RNA, argonaute protein, and other proteins are called the RNA Induced Silencing Complex (RISC). Micro RNA’s help guide RISC to messenger RNA’s. The seed, part of the micro RNA, pairs with a target messenger RNA. Targeting by a micro RNA can lead to messenger RNA to be degraded or translation from being inhibited. Antisense RNA alone is not sufficient to evoke an RNAi response because the RNA needs to go through many steps with the help of other proteins to be able to have the ability to achieve RNAi.

has to be a number of changes to the genes within a cell, before it

A biological system is considered robust if it is able to withstand a variety of perturbations such as genomic mutations or changes in its environment. The state of being robust is considered to be an inherent property of evolving and complex dynamic systems, and it has also been suggested that robustness drives evolution and has a key part to play in the survival of organisms [3].Other aspects such as modularity, decoupling and (in the case of genetic networks) the relationship of phenotypic effects and gene similarity, all lend themselves to the increased robustness of an organism. These processes, however, are not without their flaws. There is a possibility that certain control mechanisms will not be functional, leading to the progression of harmful components. This is the most prevalent in HIV infection and the development of cancers. Research into biological systems, robustness and the problems that may arise could also generate new areas for research and provide novel methods for cancer therapy. The robustness of a system is fundamentally about managing a correlation between the system and the environment and deviations from this often result in damage to the system.

Gene expression is the ability of a gene to produce a biologically active protein. This process is regulated by the cells of an organism, it is very important to the survival of organisms at all levels. This is much more complex in eukaryotes than in prokaryotes. A major difference is the presence in eukaryotes of a nuclear membrane, which prevents the simultaneous transcription and translation that occurs in prokaryotes. Initiation of protein transcription is started by RNA polymerase. The activity of RNA polymerase is regulated by interaction with regulatory proteins; these proteins can act both positively, as activators, and negatively as repressors. An example of gene regulation in cells is the activity of the trp operon. The trp

The Earth is full of complex organisms, each with specific adaptations and behavior patterns that help them thrive in their environment. In order to grow and develop into these specialized beings, something profoundly important exists at the genetic level: gene regulation. Gene regulation is the process by which living organisms alter the frequency or expression of specific portions of their DNA, occurring through many different mechanisms. This sort of genetic policing helps living creatures to coordinate specific responses to their environment, or stimulate growth and development in the most efficient manner possible. In the 1990’s, scientists thought that they had a comprehensive understanding of a multitude of regulatory mechanisms, until biologist Andrew Fire published his research outlining a previously unknown process: RNA interference.