1.1 Non-coding RNAs The central dogma of molecular biology states that genetic information is conveyed from DNA to mRNA to protein implying that proteins are the main functional genetic output (Crick 1970). Even those few early known non-protein-coding RNAs (ncRNAs) such as transfer RNA, ribosomal RNA, snoRNAs and splicosomal RNAs were in the end required for mRNA processing and translation. The dogma might still be applicable to prokaryotes whose genome consists of approx. 90 % protein-coding genes. In eukaryotes, however, only about 2 % of the genes are protein-coding (Alexander et al. 2010) and those have been studied intensively. The remaining major fraction of the genomic output has for a long time been classified as genetic junk, as most transcripts had low or no protein-coding capacity nor cis-regulatory functions. Techniques like high resolution microarray and improved sequencing assays revealed that 98 % of the human genome consists of non-protein coding sequences compared to 25 % in prokaryotes. Remarkably, this increased proportion of ncRNAs (and not the number of protein-coding genes) comes along with higher developmental complexity. When proteins reach their functional limits, other regulatory components such as introns and other sequences coding for ncRNAs evolved (Mattick 2004). Coincident with the abundance of ncRNAs, higher species possess also more proteins carrying RNA- binding sites (Mattick & Makunin 2006). The demotion of non-coding transcripts as „transcriptional noise“ had to be corrected as a significant number of non-coding transcripts showed cell type-specific expression, specific localization in cellular compartments, functional relevance for development and p...
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...s and macroautophagy A role of ncRNAs in core autophagy pathways has already been shown for more than ten different miRNAs (Frankel & Lund 2012). Just like miRNAs, lncRNAs possess transcriptional and post-transcriptional modification abilities and they are – also considering their high abundance – likely candidates regulating different stages of autophagy. Furthermore, combining the fact that both lncRNAs and autophagy have been shown to be up or down regulated in certain cancers (Levine 2007; Prensner 2011) might indicate a functional interplay of lncRNAs and autophagy. Despite the increasing number of lncRNA-related publications, there are only very few groups addressing the role of lncRNAs in autophagy: i. Zhao et al 2014, Role3 of3 lncRNA3 HULC3 in3 cell3 proliferation,3 apoptosis3 and3 tumor3 metastasis3in3gastic3cancer, Oncol Rep:
Alu elements are a class of transposable genes found exclusively in the genomic sequences of primates. Averaging in lengths of approximately 300 base pairs, Alu elements are classified as being short interspersed elements, more commonly referred to by the acronym SINEs. These elements interject themselves into the DNA sequence by means of retroposition. Once established into the genome, Alu elements are considered to be stable, only rarely being subjected to deletion. Initial studies on the prevalence of Alu inserts within the modern human genome was calculated to be nearly 5% (Comas, Plaza, Calafell, Sajantila, & Bertranpetit, 2001), however, more recent research indicates that the actual percentage of various Alu elements account for nearly 11% of the DNA sequence (Deininger, 2011). Alu elements are of great importance to scientists, particularly to those who wish to study evolution, as well as, migrational patterns of early human populations.
... in glioma cells (suppression of autophagy, mentioned above, is often accompanied by activiation of apoptosis). Silencing eEF-2 kinase expression with the inhibitors (NH125) remarkably increased the TMZ-activated apoptosis in human glioma cells. One other important discovery of this experiment was that the combination of TMZ and NH125 did not cause TMZ to destroy normal human astrocytes. Essentially, co-treatment of TMZ with NH125 made TMZ more effective against glioma and produced a better survival benefit for the mice, but could not cure the mice. This may be because the amount of NH125 (eEF-2 inhibitor) used was not enough, or the dosages of TMZ and NH125 were not optimal. Nonetheless, development of better and more effective inhibitors of eEF-2 kinase may help in finding the cure for glioblastoma multiforme, the malignant and extremely aggressive brain tumor.
Miller, Kenneth R. and Joseph S. Levine. “Chapter 12: DNA and RNA.” Biology. Upper Saddle River: Pearson Education, Inc., 2002. Print.
Ridley, who has a Ph.D. in zoology, is a big supporter of the Darwinian view of the world. He views the genome as a historical documentation of our species from its conception. He describes our evolutionary history. He tells about the mass extinctions that occurred in the past, and that it was by chance our cellular ancestors survived these events. Ridley gives us an insight into molecular biology by choosing one gene from each or our 23 chromosomes and elaborating on it. Along with evolution and microbiology, this book goes into other fields of biology, including medicine and biotechnology.
Hall, Linley Erin. “Understanding Genetics DNA and RNA.” New York: The Rosen Publishing Group, Inc., 2011. Print. 01 Apr. 2014.
Carl Woese’s (1990) groundbreaking paper categorised the Tree of Life into three domains for the first time– Archaea, Eubacteria and Eukarya. Before this, Archaea were known as Archaebacteria due to their prokaryotic, single-celled appearance similar to bacteria. However, Woese analysed 16S ribosomal RNA from all three groups and discovered there were differences of such significance in the sequences, for example between positions 180 and 197, that Archaea should be classified as their own domain. The three domains are believed to have separated from one common ancestor, with Eubacteria and Archaea diverging 3.8 billion years ago and Archaea separating from Eukarya 2.8 billion years ago. This means that, despite their appearance, Archaea share more similarities with eukaryotes, such as 33 identical ribosomal proteins, than with bacteria.
There are three main divisions of living organisms: Prokaryotes, eukaryotes and archaea. This essay will outline the division between the prokaryotic and eukaryotic organisms and explore the reasoning behind such differences with regard to general structure, storage of deoxyribonucleic acid and its replication, metabolic processes, protein synthesis and ribonucleic acid processing.
Eukaryotic cells share several distinguishing features, such as: cytoplasm within specialized organelles such as the mitochondria, chloroplast, the Golgi complex, both a rough and smooth endoplasmic reticulum, a nuclear envelope that isolates DNA from the cytoplasm, and a endomembrane system that provides structure and function to the organelles of the cell. Both the mitochondrion and chloroplast are energy transducing organelles, meaning that they transform energy from one form to another, and are believed to be evolved from free living prokaryotes as held by the theory of endosymbiosis. This theory suggests that infolding of the plasma membrane coupled with the absorption of a prokaryotic cells by other prokaryotes could evolve into a later, more complex and specialized type of cell and is proofed by related morphological features such as between cytobacteria and chloroplasts, and between mitochondria and aerobic prokaryotes. Further substantiation includes mitochondria and chloroplasts reproduction through binary fission like prokaryotes, the presence of DNA in both free living prokaryotes and in energy transducing organelles (apart from in the nucleus), protein synthesis and the presence of enzymes and ribosomes where the ribosomes of prokaryotes are comparable to those in mitochondria and chloroplast,
Nikitina, E. G., Urazova, L. N., & Stegny, V. N. (2012). MicroRNAs and Human Cancer.Experimental Oncology, 34(1), 2-8. Retrieved from http://archive.nbuv.gov.ua/portal/chem_biol/eol/2012_1/002.pdf
An idea first brought to the attention of the world back in the 1960’s when researchers first noted that the cell could destroy its own contents by a matter of enclosure within the membrane. (1) This lead to the formation of vesicles that were efficiently transported to a recycling component called the lysosome, for degradation. The term autophagy simply means "self-eating”. Scientifically, the term accounts for “a normal physiological process that deals with the destruction of cells in the body”. (2) Due to the complexity of the phenomenon, little advances had been made until a series of experiments were conducted in the early 1990’s. Yoshinori Ohsumi; a Japanese cell biologist born in 1945, conducted an experiment using the test subject of yeast, which led him to identify the critical genes for autophagy. Through further studies, he noted the underlying correlation between autophagy mechanisms used in yeast and the machinery used in our cells. Ohsumi’s new discoveries created the path in understanding the critical importance of autophagy in many
Almost all biology students learn the fundamentals of gene expression, DNA contains information which is transcribed into RNA to create protein. Students however, are not taught of RNA Interference, the biological process where RNA molecules inhibit a gene’s expression, RNAi for short. While RNAi is a fairly new discovery, its use in modern biological research is groundbreaking. RNA Interference works by binding Double-stranded RNA molecules (siRNA) to a complementary messenger RNA. The enzymes Dicer and Slicer then cleave the chemical bonds which hold the messeger RNA in place and prevent it from delivering protein silencing instructions thus, the term, Gene Silencing. This phenomenon was first discovered by Richard Jorgensen in 1990 when he was trying to produce deeper purple colored petunias by introducing more purple pigment genes to the flower. To his surprise, the purple petunia turned completely white and got the opposite of his predicted result. At the time Jorgensen coined this effect, “Cosuppression”. It was not until 1998 that Andrew Fire and Craig, C Mello explained the process of RNAi and discovered its use in Caenorhabditis elegans (C. Elegans). In 2006 Fire and Mello won the Nobel Prize in Physiology or Medicine “for their discover of RNA Interference – gene silencing by double stranded RNA”. They utilized the nematode, C. Elegans due to its whole genome being sequenced. This unique characteristic allows for every gene to be tested
... to RNA and the translation to proteins, as well as gene expression. Noble does an excellent job of presenting an opposing view to the central dogma of biology, using metaphors to attempt to make his differing views clearer to the reader. While Noble does use a lot of scientific evidence to support his opinions, his use of metaphors is overwhelming and it can easily distract the reader from the point that he is trying to make. ,Nobles’ explanations of gene expression help the reader to understand the process of evolution, giving a more or less clear view as to how redundancy in the genome can lead to variation. Noble neglects, however, to expand upon natural selection or any other ideas related to evolution. If these ideas were present, they were lost somewhere between the overwhelming use of metaphors and the overly detailed explanations of cell signaling processes.
The two most advanced and scientifically supported hypotheses of evolution from a prokaryote precursor to a eukaryote are The Theories of Endosymbiosis and Autogenesis. The hypotheses both base their claims on the fact that eukaryotic genomes are chimeric, they don’t have a vertical lineage from one common ancestor, but rather a varying ancestry with diverse lineages of archaea and bacteria. Endosymbiosis is the idea that one prokaryotic organism engulfed another which formed a symbiotic relationship between the two, leading to the creation of the eukaryote and its hallmark semi-autonomous organelles (Sagan 1967). Autogenesis is
Distinct characteristics are not only an end result of the DNA sequence but also of the cell’s internal system of expression orchestrated by different proteins and RNAs present at a given time. DNA encodes for many possible characteristics, but different types of RNA aided by specialized proteins sometimes with external signals express the needed genes. Control of gene expression is of vital importance for an eukaryote’s survival such as the ability of switching genes on/off in accordance with the changes in the environment (Campbell and Reece, 2008). Of a cell’s entire genome, only 15% will be expressed, and in multicellular organisms the genes active will vary according to their specialization. (Fletcher, Ivor & Winter, 2007).