DNA and RNA are involved in the synthesis of proteins.
A segment of DNA that contains the recipe for building one protein is called a gene.
Fig. 8: Enhancers and DNA-Bending Proteins Initiating Transcription
While most assume that gene expression is largely regulated in the nucleus at the level of transcription, it turns out that a myriad of mechanisms can act to control gene expression post-transcriptionally. In my lab we are interested in understanding the molecular mechanisms that function to regulate gene expression in the cytoplasm. In the cytoplasm RNA-binding proteins and regulatory mRNAs act to control of mRNA translation, stability and subcellular localization by binding to target mRNAs. A typical eukaryotic genome encodes several hundred RNA-binding proteins and regulatory RNAs highlighting the wide-spread nature of post-transcriptional control. While it is clear that these type of regulatory circuits are very important, the molecular mechanisms involved and their biologic significance remain largely uncharacterized. We use the early Drosophila (fruit fly) embryo as a model system and a combination of biochemical, genetic, cell biologic, genome-wide and computational methods in our work.
Other potential mechanisms that may play a role incancers with RP mutations and in the ribosomopathies are related tothe hypothesis that defective maturation of ribosomal subunitscould delay translation of certain mRNAs or that malfunction ofaccumulated ribosomal precursors may cause aberrant translation(reduced fidelity). It may involve differential translation ofspecific mRNA transcripts or the use of alternative translationinitiation sites. Both quantitative variations in actual ribosomenumbers and qualitative alterations such as lack of rRNAmodifications of the ribosomes have been reported. A first exampleis X-linked DKC, caused by a mutation in , which encodesdyskerin (). Nucleolar dyskerinassociates with a specific group of snoRNPs known as H/ACA, whichfunction in the pseudo-uridylation of rRNAs, but mutant DKC1 altersthe rRNA pseudo-uridylation pattern of ribosomes reducingtranslation of some mRNAs (). Asecond example is fibrillarin, a nucleolar rRNA methyl-transferase(). p53 represses fibrillarinby direct protein-protein interaction and high levels offibrillarin are accompanied by abnormal rRNA methylation patternsand impaired translational fidelity (). In this setting, p53 acts as asurveyor of protein synthesis by its ability to regulate ribosomeactivity (). The translationfidelity model has gathered additional experimental evidence. TheRPL10 Arg98Ser mutant, the most commonly identified ribosomalmutation in acute T-ALL, was functionally evaluated in yeast(). The mutation leads to afailure to produce 60S followed by degradation of the defectiveribosomes (). The 60S subunitshortage puts pressure on cells to select for suppressors of theribosome biogenesis defect, allowing the yeast cells to boostribosome production to sustain cell proliferation (). However, the consequence of thisbypass is synthesis of defective ribosomes that wreak havoc in themRNA translation process ().Whether similar mechanisms exist in humans and how they functionremains to be investigated. It is interesting to note that some ofthe RPs mutated in cancer including RPL5, RPL10 and RPS20 are knownto bind directly to mRNAs, moreover, two of them RPL5 and RPL10,have a preferential association with monosomes reflecting ribosomeheterogeneity ().
Genetic Control of Protein Synthesis, Cell Function, …
Amsterdam A, Sadler KC, Lai K, FarringtonS, Bronson RT, Lees JA and Hopkins N: Many ribosomal protein genesare cancer genes in zebrafish. PLoS Biol. 2:E1392004. : :
From studies on the ribosomopathies it is clearthat impaired ribosome biogenesis is to be considered a risk factorfor cancer initiation. Remarkably, distinct and recurrent mutationsin genes encoding for ribosomal proteins (RPs) have recently beenimplicated in cancer development in patients without a previousknown history of a ribosomopathy. This has been a wake-up call inthe tumor biology field and one may compare this with the paralleland equally remarkable discovery of histone H3.3 mutations inpediatric gliomas (). Therole of RPs in cancer is a complex issue and while some exert adirect effect on proto-oncogenes and tumor suppressor genes, p53, it is possible that mutations in other RPs mayhave general effects on mRNA translation. The trend evident fromthe assembled sequencing data suggests that RP mutations or changesin the expression patterns of RPs could be functionally relevant ina large number of cancer types and cases. A more complete pictureof the relevant RPs in cancer is due to emerge from additionalcancer genome analysis projects and functional studies.
The genetic control of protein synthesis: The …
I joined the Biochemistry Department at the UofT in 1999. How did I get here? After a youth spent reading sci-fi and playing D&D, I received my Ph.D. from McMaster University in 1994 where I worked with James Smiley to understand the molecular mechanisms that regulate cellular and viral gene expression in cells infected with Herpes simplex virus. It was during this time that I developed an interest in understanding the molecular mechanisms that control mRNA translation, stability and subcellular localization. I continued to pursue this interest as a post-doctoral fellow at Stanford University in Paul Macdonald’s lab using the fruit fly embryo as a model system. While at Stanford I discovered the highly conserved Smaug family of RNA-binding proteins that they regulate the translation and stability of target mRNAs.
In the cytoplasm gene expression is regulated by RNA-binding
proteins and regulatory RNAs (represented by the coloured balls)
that interact with target transcripts to control mRNA subcellular
localization, translational and degradation.
The genetic control of protein synthesis: The haemoglobin model
Genetic Control of Protein | Mitosis | Ribosome
Since enzymes are proteins, an error in the gene for that enzyme could render the enzyme non-functional.
31/07/2010 · Cell genes control protein synthesis
Genetic Control of Protein Synthesis Flashcards | Quizlet
2. the cell and its function and genetic control of protein
the cell and its function and genetic control of protein 1
Unit 6 DNA, RNA, Protein Synthesis
Our genetic identity is "coded" in the sense that four building blocks, called nucleotides, string together to spell out a biochemical message—the manufacturing instructions for a protein.
Protein synthesis :: DNA from the Beginning
Enhancers are regulatory proteins that bind to DNA located some distance from the operon they control by working with DNA-bending proteins. The DNA-bending proteins bend the DNA in a way that now allows the enhancer to interact with the promoter in such a way that RNA polymerase can now bind and initiate transcription.
RNA acts as the information bridge between DNA and protein
are regulatory proteins that bind to DNA located some distance from the they control by working with DNA-binding proteins. The DNA-bending proteins bend the DNA in a way that now allows the enhancer to interact with the in such a way that RNA polymerase can now bind and initiate transcription (see Fig. 8).
Genetic noise control via protein oligomerization
Congenital diseases found in humans that are linkedto genetic defects in RPs or ribosome biogenesis factors arecollectively known as the ribosomopathies (–).These include Dyskeratosis congenita (DKC), Diamond-Blackfan anemia(DBA), and Shwachman-Diamond syndrome (SDS) that constitute majorinherited bone marrow failure syndromes (). The ribosomopathies arecharacterized by a number of abnormalities including birth defectsand anemia (). DBA is adominant autosomal bone marrow failure syndrome associated withmutations in RP genes including (,,–).Patients with DBA experience a block in erythroid progenitor celldivision in the bone marrow coupled to an increased apoptosis(). DBA patients have a 5-foldhigher lifetime risk of cancer than the general population,specifically a 28- to 36-fold higher risk of developing AML,osteosarcoma, or colon cancer ().Although a somatic mosaic disorder, and not congenital, heterozygous loss is associated with syndrome and the development of anemia (). Patients with 5q- syndrome or SDSare at higher risk of developing AML (–).DKC is a syndrome characterized by premature aging and increase incancer susceptibility. X-linked DKC, which has a more severephenotype compared with the autosomal dominant form of DKC, iscaused by a mutation in , which encodes dyskerin(). Dyskerin is in part anucleolus located protein associated with the snoRNPs involved inrRNA modification (,). Patients with X-linked DKC arepredisposed to AML, lymphoma, and a variety of solid tumorsincluding squamous carcinoma (). Note that both DKC and SDS have ahigher risk of cancer development than DBA, especially the risk ofleukemia, although some cohorts are rather small thus causingestimates with greater differences among the studies (,,,,).It should be emphasized that the main problem in DBA patients isrelated to acute effects from bone marrow failure or complicationsdue to chronic blood transfusions and not cancer ().
1. Genetic Control of Enzyme Synthesis through …
The basis of protein synthesis is the translation ofmessenger RNA (mRNA) to an amino acid sequence. Translation of mRNAis carried out by the ribosome, transfer RNA (tRNA), with theassistance of an army of different helper proteins. The intrinsiccatalytic activity of ribosomes is thought to be dependent onribosomal RNA (rRNA), that is involved in mRNA decoding andformation of peptide bonds. Certain chemical modifications on rRNA,including pseudo-uridylation and ribose methylation, are criticalfor maintaining proper rRNA structure and modulate the interactionsbetween rRNA and proteins (). Theribosome consists of two subunits, each of which is made up ofribosomal RNA (rRNA) and many RPs. Eukaryotes have 80S ribosomes,consisting of the small (40S) and the large (60S) subunit. Thelarge 60S subunit is composed of a 5S rRNA, a 28S rRNA, a 5.8Ssubunit, and ~46 RPs. The small 40S subunit has an 18S rRNA and ~33RPs. Note that the 5S rRNA is transcribed by RNA polymerase III,while 28S, 5.8S, and 18S rRNAs are processed from a long precursor(pre-) rRNA transcribed by RNA polymerase I (). The maturation of pre-rRNA occurs inthe nucleolus involving both endo- and exonucleases that removeexternal and internal transcribed sequences. In the nucleolus the45S pre-RNA associates with RPs, ribonucleases, RNA helicases,small nucleolar RNPs and other accessory factors, to form 90Spre-ribosomes. During the maturation process, the 90S pre-ribosomeis separated into pre-40S and pre-60S subunits that are exported tothe cytoplasm where maturation is completed (). It should be noted that RPs aresynthesized by pre-existing ribosomes in the cytoplasm and importedinto the nucleus where majority of the RPs home into the nucleolusto assemble with rRNA, and majority of RPs are essential inribosome biogenesis (–). Strikingly, RPs have highisoelectric points allowing them to interact with rRNAs, mRNAs, andtRNAs (). The names of the RPsbelonging to the large subunit include the prefix L and the namesof the RPs of the smaller subunit include the prefix S. A newuniversal nomenclature has been launched and we will provide bothnames at their first mentioning in the text ().
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