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This Protein In Your Brain Could Be At The Heart Of Creating Memories Assignment Sample

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This Protein In Your Brain Could Be At The Heart Of Creating Memories

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Introduction

The brain is performed the high-end task which is made up of a massive neural network. Effective and precise working reflects modulating the neurons' structure, which helps achieve a dynamic and active balance between plasticity and long-term memory creation. The balance-achieving process includes local translation and mRNA localisation. This requires coordination between regulatory non-coding RNA and RNA binding proteins (RBPs). The researcher has found a mysterious protein named Staufen homolog 2 (Stau2), which interacts with RBPs and target mRNAs. Stau2 is a double-stranded RNA, which binds with proteins and is responsible for the localisation and/or transportation of mRNA in various sub cellular organelles and compartments. A news article has been considered, which has been criticized in science mass media:

“This Protein in Your Brain Could be at the Heart of Creating Memories”. In this literature review, mainly three primaries and one secondary article have been selected to discuss Stau2 activity in memory creation within the brain by RNA localization. Synaptic plasticity development with Stau2 has been elaborated by considering information from four articles to describe long-term molecular alteration and its effect on brain memory. This information has been organized from article content, methodology, experimental design and comparative conclusion.

Staufen homolog 2 in memory creation

Staufen homolog 2 is present in the cytoplasm; however, the protein displays nucleolar transfer or localisation. Stau1 expression is ubiquitous, while Stau2 expression is limited to heart and brain function (Ravanidis et al. 2018). Stau2 is a binding protein, which are involved in “posttranscriptional regulation” which helps in gene expression. Controlling this Stau2 is crucial in progression of cell cycle, which help in division of non-neuronal cell. RBPs act as assembling proteins for RNA with ribonucleoprotein, which mediate the gene expression that adjoints with neuron expression. Article 1 discussed about brain architecture and complexity depending on neuron expression (Popper et al. 2018). This primary article highlights Stau2 expression in controlling neutrons. Article 1 describes that complex neuronal circuit is a key component of memory formation and learning. Cortical neurogenesis occurs with the help of Stau2, and neurogenetic progenitor cell differentiation of mRNA takes place. Therefore, synaptic signal dependent on mRNA localization in dendrites occurs. Researchers enclosed information about RNA granules consisting of Stau2 from rat brains having higher transcripts, which facilitates the production of better synaptic function. A researcher has experimented with the suppression of Stau2 protein in the rising of depression (Popper et al. 2018). Primary article 1 mainly concentrates on the consequences of observation on Stau2 insufficiency. On the other hand, considered primary article 2 focused on binding Stau2 with RBP 9 and FNE (Grzejda et al. 2022). As per article 2, there are two distinct granules formed by Staufen homologous 2 with RBPs. One is large, which is incapable of transporting mRNA and remains within the

“rough endoplasmic reticulum (RER)” and another is a small granule, which actively takes part in the transportation of mRNA from the soma of neurons to dendrites. Therefore, denaturation of Stau2 produces a significant effect on dendritic arborization and memory deficit.

Considered four articles were collected from peer-reviewed journals. Therefore, the validity of these journals is high, which is also acceptable to biology audiences. Article 3 provides comprehensive information about dendritic mRNA encoding with RBPs in RNA granules along with Stau2. As mentioned by Ohashi and Shiina (2020), mRNAs are localised from soma to

the "dendrite-enriched stratum radium layer (SR)" by considering RNA sequencing. In this process, within the

“hippocampal CA 1” region, soma gets aligned with

“stratum pyramidale (SP)”. Thereafter, within neurons, dendrites get elongated into stratum radiatum. The author describes that within the SR layer of hippocampal CA1 in rats, mRNA is present in higher concentration while SP layers consist of lower concentration of mRNA. However, after mRNA localisation in RNA granules, mRNA concentration reduced significantly, showing long-term memory impairment in rat models. While discussing RNA granules, the researcher mentions that in Drosophila, the role of Stau2 is in memory creation. During embryo development, synaptic plasticity demands Stau1 and Stau2. In the deficiency of Stau1, only memory formation is observed to be poor, while in the deficiency of Stau2 various types of memory are affected in the mice model. In knockout mice, it has been observed that spatial working memory is impaired due to stau2. The temporal association is also 'incomplete with increasing insufficiency of Stau2. Similarly, as Ravanidis et al. (2018) state, alteration of mRNA processing produces temporal silencing, polyadenylation, translation and target localisation events. Therefore, Stau2-oriented molecular alteration changes mRNA localisation and causes gene alteration. This eventually troubled memory formation within the brain due to inappropriate synaptic plasticity.

Researchers of articles 1 and 2 use animal models; however, article 1 is only based on the mouse model, while Article 2 is based on outcomes observed from the mouse and Drosophila model. The conclusion of article 3 has been established by experimenting on mice models. The researcher has considered knockout mice to build a link between mRNA binding proteins, Satu2 and the regulation of mRNA (Ohashi and Shiina, 2020). On the other hand, a secondary article has been considered in which various Stau2 protein activity-related concepts have been reviewed in the context of regulating brain and memory function. In article 1 researcher has Approval from an institution to perform experiments on an animal model in order to avoid animal protection-related ethical issues (Popper et al. 2018). 5 generations of Stau2 mice have been observed. Behavioural analysis has been performed in 4 months old Albany mice. Mice were placed in pathogen-free conditions in 2 to 5 groups of the same gender. A controlled environment was maintained before behavioural analysis, which included 12 hours of the dark and light environment with free access to water and food. Therefore, highly professional animal handling knowledge is required to obtain the expected result. On the other hand, Drosophila Melanogaster files have been used in pairs to find the mimi scaffold neuronal granules and Stau2 relation for the experiment. Delicate handling is required for raising flies and the authors mentioned that 25oC temperature had been maintained for raising Drosophilas.

Stau2 and radial glia expression are relative to neuron functioning. According to a secondary article produced by Meservey et al. (2021), asymmetric division cause mRNA localisation, which RBP Staufen2 regulates within the

“apical process of radial glia”. Radial glia is neural stem cells in developing embryonic brain cells. As opined by Llinares-Benadero and Borrell (2019), in cerebral cortex development, radial glial cells play a crucial role. Additionally, glial cells act as scaffolds while migrating neurons and cerebral cortex architecture. From radial cells, progenitor cells and primary stem cells of the brain are formed. Therefore, radial glial cells are indirect or directly related to neuron function (Schieweck et al. 2021). A secondary type of article encapsulates mRNA transportation which relies on stau2 and RBPs. In response to extrinsic and intrinsic cues in the apical process of radial glia, asymmetric cell division is observed, producing new radial glia, either intermediate progenitor cells or terminally differentiated neurons. Apical end feet are enriched with Stau2 which extensively helps in forming a complex with DDX1 and Purnilio 2. Ultimately, it helps in the localisation of mRNAs. On the other hand, the results section of a primary research article indicates that Purnilio 2 (Pum 2) and Staufen homologous 2 affect neuronal gene expression (Stau2). After the transduction of cortical neurons during the polysome-profiling step, it has been found that paired mRNA sequencing is produced. Both Pum 2 and Stau2 act as selective regulators in neuronal proteome expression. However, Stau2 preferentially controls and regulates mRNA, while Pum2 is responsible for activating the translation. Hence, it can be discussed that Staufen 2 creates a selective balance in the synaptic proteome. 

Article 1 is well structured and consists of information regarding Stau2 lacking effect in Mice models, which can be further used to relocate the mRNA expression oriented to RBP and Satu2 in human subjects. However, in article 1, theoretical knowledge is limited. On the contrary, the article 2 researcher has produced a contrasting knowledge on mRNA granule formation with the help of Stau2. Article 3 theoretical framework roots for RNA sequence available in the hippocampus in mice model that has an association with long-term memory impairment with reduced mRNA expression. For findings, this association reverse transcript polymerase chain reaction has been performed on isolated RNA from a knockout mice model (Ohashi and Shiina, 2020). Therefore, these primary articles, along with mice and the drosophila model, are for further research to reveal a pathway of synaptic plasticity and the role of Satu2 in brain function. The secondary type of article is not well structured as the review method s poor. However, information regarding Stau2 and memory formation in terms of radial glial at the embryo level has been explained well. Article 1 encapsulates behavioral change information in mature mice (Popper et al. 2018). Henceforth, a secondary article can be considered to link memory formation from the embryo level to the mature level.

The methodology that has been followed for article 1 is experimental research, which is similar to article 2 and article 3. The aim is to analyze the correctness of the concept of a particular protein named Stau2 in synaptic plasticity and responses towards long-term depression. However, three primary articles lack a hypothesis, which indicates low internal validity for the study. Similarly, the secondary article review process is unambiguous, reducing the article information's reliability (Meservey et al. 2021). Among considered, the primary articles' methods are transparent, which includes an explanation regarding the use of polymerase chain reaction, transcriptase PCR, western blotting test and others. However, article 3 methodology is unequivocal (Ohashi and Shiina, 2020). On the contrary, in secondary articles, results and important components have been represented in tabular format. The secondary article is beneficial to educate novice people about the role of Staufen homologous 2 at the embryonic level in mRNA expression. Article 1 produces a piece of relational information regarding deficiency of Stau2 protein in increasing chances of depression which has been assessed by observing a behavioural change in performance in mature mice. Article 3 experimented on Drosophila, highlighting how neuronal granule formation is dependent on RBP and stau2. Pathway description is elongated in article 3 with respect to the mice model. Therefore, irrespective of the limitations of these article structure and results, information is well related to describe to the biology audience that lack of neuronal granules expression causes depression and long-term potentiation (LTP).

Four articles have been comparatively analysed, which produces transparent knowledge about neuronal granules and Stau2 association in depression and memory. Various pictorial descriptions have been used, which helped in describing Satu2 expression in mRNA localisation, which researchers have obtained. As opined by Fernández-Moya et al. (2021), Stau2-enriched RNA duplexes cause dendritic localisation, which facilitates mRNA transcription. Therefore, brain learning depends on the expression of mRNA. Similarly, as stated by Sears, J.C. and Broadie (2020), negative feedback is provided by FMRP PKA, which affects RNP processing related to staufen 2. This negative feedback is required in RNA binding defibrillation, which hampers learning capability. Henceforth, a significant relationship is present between Staufen 2 and depression along with learning capability of the brain.

Conclusion

It can be concluded that a comparative analysis has been performed between four articles to formulate a well-structured literature review. A biological scientific report has been established using three primary and one secondary article containing information about the role of Stau2 expression in depression and LTP. Literature findings significantly highlight that a lower concentration of Stau2 causes high depression as synaptic plasticity is reduced, which causes the transmission of fewer currents from one neuron to another. The selected articles are valid as these are selected based on peer reviewed. Additionally in the selected primary article, authors used mice and drosophila model, which will be helpful for future research. Therefore, a reduced concentration of Stau2 in RNA granules causes less memory formation, decreasing performance. These literature findings demonstrate the association between Staufen2's roles in memory development; however, the neuronal pathway is not well established.

Reference list Selected article

  • Article 1: Popper, B., Demleitner, A., Bolivar, V.J., Kusek, G., Snyder-Keller, A., Schieweck, R., Temple, S. and Kiebler, M.A., 2018. Staufen2 deficiency leads to impaired response to novelty in mice. Neurobiology of Learning and Memory, 150, pp.107-115
  • Article 2: Grzejda, D., Mach, J., Schweizer, J.A., Hummel, B., Rezansoff, A.M., Eggenhofer, F., Panhale, A., Lalioti, M.E., Cabezas Wallscheid, N., Backofen, R. and Felsenberg, J., 2022. The long noncoding RNA Mimi scaffolds neuronal granules to maintain nervous system maturity. Science Advances, 8(39), p.eabo5578.
  •  Article 3: Ohashi, R. and Shiina, N., 2020. Cataloguing and selection of mRNAs localized to dendrites in neurons and regulated by RNA-binding proteins in RNA granules. Biomolecules, 10(2), p.167.
  • Article 4: Meservey, L.M., TopCar, V.V. and Fu, M.M., 2021. mRNA Transport and Local Translation in Glia. Trends in Cell Biology, 31(6), pp.419-423.

Other

  • Fernández-Moya, S.M., Ehses, J., Bauer, K.E., Schieweck, R., Chakrabarti, A.M., Lee, F.C., Illig, C., Luscombe, N.M., Harner, M., Ule, J. and Kiebler, M.A., 2021. RGS4 RNA secondary structure mediates Staufen2 RNP assembly in neurons. International journal of molecular sciences, 22(23), p.13021.
  • Llinares-Benadero, C. and Borrell, V., 2019. Deconstructing cortical folding: genetic, cellular and mechanical determinants. Nature Reviews Neuroscience, 20(3), pp.161-176.
  • Ravanidis, S., Kattan, F.G. and Doxakis, E., 2018. Unravelling the pathways to neuronal homeostasis and disease: mechanistic insights into the role of RNA-binding proteins and associated factors. International journal of molecular sciences, 19(8), p.2280.
  • Schieweck, R., Ninkovic, J. and Kiebler, M.A., 2021. RNA-binding proteins balance brain function in health and disease. Physiological reviews, 101(3), pp.1309-1370.
  • Schieweck, R., Riedemann, T., Forné, I., Harner, M., Bauer, K.E., Rieger, D., yee Ang, F., Hutten, S., Demleitner, A.F., Popper, B. and Derdak, S., 2021. Pumilio2 and Staufen2 selectively balance the synaptic proteome. Cell Reports, 35(12), p.109279.
  • Sears, J.C. and Broadie, K., 2020. FMRP-PKA activity negative feedback regulates RNA binding-dependent fibrillation in brain learning and memory circuitry. Cell reports, 33(2), p.108266.
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