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Describe the role of DNA in protein synthesis
RNA traffic in neurons. As shown inFig. 1, at the time oftranscription, nascent RNA was already complexed with RNA-bindingproteins (RBPs) to form RNA-protein particles (RNPs), which thenmigrate to the cytoplasm through the nuclear pore complex. In thecytoplasm, through interaction with motor proteins, RNPs aretransported to their final destinations, where they can pause in asilent state, until they are activated by a signal. Some componentsof RNPs can then be cycled back to the nucleus. When exiting thenucleus, however, two different peripheral destinations areavailable to RNPs: a) dendrites or b) axon. Localized translationof mRNA may be controlled by synaptic activity (action potential).In response to neurotransmitters and/or neuromodulators, which bindto their receptors on the post-synaptic element, signaltransduction pathways can be activated (red dotted lines), whichtarget RBPs, inducing post-translational modifications, such asphosphorylation. RBP modifications in turn cause remodelling of theRNPs, with the release of some RBPs and recruitment of mRNA toribosomes. Newly synthesized proteins accumulate at thepost-synaptic sites, thus inducing long-lasting modifications. SVs,neurotransmitter-containing synaptic vesicles. Synthesis,maturation, and transport of RNPs are shown as in Fig. 1.
Musashi-1 (Msi1) RBP was first reported to play arole in the development of the adult externalsensory organ (). Inmammals, Msi1 is considered a specific marker for neural/progenitorstem cells (–). It acts by suppressingtranslation of mRNAs encoding differentiation-inducing proteins,such as the membrane protein Numb which is involved in theNotch/Delta signalling cascade (,,,), and the cyclin-dependent kinaseinhibitor p21 ().
" The Three Roles of RNA in Protein Synthesis; H ..
During development, neurons sprout processes orgrowth cones, which explore their environment and guide pathfindingover extremely long distances. It is now clear that at least someaspects of axon guidance require axonal mRNA translation (–,–). For example, Welshhans andBassell developed and used a new turning assayallowing these authors to demonstrate that growth cones exhibitprotein synthesis-dependent attraction to netrin-1 and BDNF. Thisattraction is lost in neurons lacking ZBP1; concomitantly,BDNF-induced β-actin mRNA localization is also attenuated. ZBP1 isalso necessary for netrin-1-induced local translation of β-actinmRNA ().
Localization and translation of mRNA in axons stillpose two main problems. The first one concerns the organization andregulation of the translational machinery: axoplasm structuraldomains have been recently described (periaxoplasmic ribosomalplaques: PARPs) which contain ribosomes attached to a superficialplaque-like structural matrix, together with β-actin mRNA, ZBP-1,SRP54, myosin Va and kinesin II molecular motor proteins. Rapidaxoplasmic transport of microinjected heterologous radiolabeled BC1RNA to putative PARP domains suggested that the anchoredtranslation machinery potentially represents the destination ofspecifically sorted mRNAs (). Moreover, multiple translationcomponents, including ribosomal subunits and initiation factors,interact with the trans-membrane receptor (DCC) for netrin-1,suggesting that their activity can be regulated by extracellularsignals (). The possibilitythat ribosomes/mRNAs could be at least in part horizontallytransferred into axons from surrounding glial cells was alsodiscussed (,). In addition, it has been reportedthat proximal segments of transected sciatic nerves accumulatenewly synthesized RNA in axons, and that these mRNAs are actuallysynthesized in Schwann cells and then transferred to neuronsthrough a mechanism that requires actin cytoskeleton and myosin-Va().
Transcription is the first of overall two protein synthesis steps
As mentioned, nELAV proteins are considered earlymarkers of neuronal commitment and are expressed in a specifictemporal order in the developing nervous system of vertebrates. Inthe adult mouse, specific patterns of expression of each nELAVmember have been reported in different neuronal types, both in thecentral and peripheral nervous systems, thus suggesting a role ofnELAV proteins in the maintenance of various types of postmitoticneurons: for instance, HuC is strongly expressed in all neurons ofneocortex, while HuD is prevalent in the large projection cells ofthe internal pyramidal layer, and HuB is detectable only inscattered neurons (,).
When discussing mRNA localization determinants inneurons, a challenging issue comes from the finding that mRNAs canbe also localized in axons. For a long time, this possibility wasnot considered since the translational machinery did not seem to bepresent at significant levels in axons. Moreover, mechanismsensuring protein transport from cell bodies to the axonalcompartment were, on the contrary, present and efficient, thusmaking apparently unnecessary localized protein synthesis. However,findings of previous studies have demonstrated axonal localizationand translation of several mRNA (–), including the β-actin mRNA(–), which depends on the zipcoderecognized by ZBP1 for localization ().
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027 - Part 2 DNA & RNA — bozemanscience
Mature transcripts can be localized through at leastthree mechanisms: i) local protection from degradation, ii)diffusion and local anchoring, and iii) direct transport byinteraction with the cytoskeleton and cytoskeleton-associated motorproteins (–). Subcellular pre-localization ofmRNAs and locally regulated translation offer cells at least threeimportant advantages: i) energy saving: a high number of proteinmolecules can be obtained locally by transporting and translating asingle mRNA molecule; ii) efficacy/safety of protein production:some proteins may be harmful to the cells when synthesized in theincorrect location; the myelin basic protein (MBP), a majorcomponent of the axon-wrapping myelin sheet, produced in thecentral nervous system (CNS) by oligodendrocytes, is, for example,a sticky protein that potentially interacts with any cell membraneif produced in the cell body (,,); other proteins, such as actin,tubulin and microtubule-associated proteins, exist as differentisoforms, all able to form multimers/polymers; their localizedsynthesis allows the formation of only the right multimers; iii)differential translation regulation: in response to localsignaling, proteins may be synthesized only in the compartmentexposed to the signal (,).
DNA and RNA structures - What is Life HOME
Another well-studied factor involved in mRNAlocalization and, probably, modulation of translation is thealready mentioned HnRNP A2 which binds MBP mRNA, allowing itscorrect localization in the oligodendrocyte processes in whichmyelination occurs (). hnRNPF has been found to be a component of MBP transport granules, andto cooperate with HnRNP A2 in regulating MBP expression. Activityof this factor is controlled through phosphorylation by the Fynkinase (). HnRNP A2 wasfound in dendrites, in association with other hnRNPs, in largemacromolecular complexes (neuronal transport granules) that containmRNA, pre-mRNA splicing factors, and mRNA export factors (). The presence of proteins withdifferent roles in RBP granules is a common observation: forexample, the complex responsible for dendritic targeting of aCaMKII reporter contains PSF (polypyrimidine tract-bindingprotein-associated splicing factor), hnRNPU and Staufen 1RNA-binding proteins ().
DNA is a long polymer made from repeating units called nucleotides
Another domain, found in RBPs as well as inDNA-binding proteins, is the cold-shock domain (CSD), firstidentified in bacterial RNA chaperones and then found in a numberof eukaryotic proteins (Y-box proteins), which is able to interactwith single-stranded DNA and/or RNA (). In one of the best studiedCSD-containing proteins, the Xenopus protein FRGY2, the CSD wasshown to be important for the sequence-specific RNA-binding, whilea second tail domain was involved in translation repression(). Y-box protein (YB)-1, theprototypic member of the CSD-containing protein family, is both atranscription factor and a major component of mRNPs. We recentlydemonstrated that in nuclear extracts from rat brain, YB-1interacts with a group of proteins that bind the mRNA encoding thehistone variant H1°. Among these proteins another CSD-containingprotein, CSD-C2, also known as PIPPin (), was present ().
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