Heterogeneous Ribonucleic Proteins ( Hnrnps )

The small ribosomal subunit, amongst other things, is initiates the engagement of the mRNA and is responsible decoding the genetic information during translation [4].

To develop nursing career in an environment that offers tremendous potential for professional growth and achievement; exploring opportunities offered with impactful challenges utilizing my experience, skills and passion.

Neurological disorders such as Alzheimer’s disease, autism spectrum disorders (ASD), and schizophrenia impact behavior and cognitive processes. While the symptoms for these diseases vary, they share disruptions in synapse development and spine formation. In the mammalian nervous system, dendritic spines are small, dynamic protrusions on neurons that develop in response to increased presynaptic activity. Although spine dynamics throughout development have been well studied, very little is known about the genes involved in spine formation. A recent study in our laboratory discovered spiny projections on a group of inhibitory neurons called DD neurons in C. elegans. Using C. elegans as a model system, the goal of this project is to identify genes responsible for dendritic spine formation. Specifically, I will 1) conduct a forward genetic screen and examine candidate axon guidance molecules to identify genes involved in dendritic spine formation, and 2) examine the effect hyper- and hypo-presynaptic activity has on the development of spines using locomotory changes, such as thrashing and microfluidic assays, and cell-specific changes using channel rhodopsin and temperature sensitive alleles. Given the strong homology between C. elegans and mammalian genes, this research will help identify conserved mechanisms underlying spine formation and maintenance. Ultimately, understanding spine development will help shape the treatment and prevention of

Recent advantages in genome-wide analyses have revealed that roughly 90% of the human genome is transcribed, yet less than 3% of the genome consists of protein-coding genes (Wu et al., 2013). The remaining genes are transcribed as noncoding RNAs (ncRNAs), which resemble mRNA in length and splicing structures yet do not encode any proteins (Wu et al., 2013). It has been debated whether all of the ncRNA transcripts are functional due to their low expression levels and low evolutionary conservation. However, many functional ncRNA have

Most genes in plants and animals contain regions that code for polypeptides, called exons, with noncoding sequences called introns in between. Both introns and exons are transcribed from DNA to RNA, then RNA splicing occurs to remove the introns. Introns can contain nucleotide sequences that regulate gene activity. The splicing process may contribute to controlling the flow of mRNA from nucleus to cytoplasm. Sometimes splicing occurs in different ways, to produce different mRNA molecules from the same transcript.

Introduction. Dysregulation of β-cat causes abnormal brain development (121-123) and defective dendritic morphogenesis (124, 125). By interacting with N-cadherin, β-cat shapes synaptic structure (83, 84) and regulates excitatory postsynaptic strength (126, 127). In addition, the axonal localization and translation of β-cat modulate presynaptic vesicle release (128-130). As a consequence, abnormal levels of β-cat in different brain regions or circuits lead to impaired memory (12, 131, 132), and a depression-like phenotype (91). However, the circuitry mechanisms for how β-cat dysfunction leads to the pathogenesis of ASDs are largely unknown. An imbalance of excitatory and inhibitory signals has been implicated in the pathophysiology of

John F. Kennedy once said “Change is the law of life. And those who look only to the past or present are certain to miss the future.” As imaging becomes better, our understanding of how neurons work, and the human brain will improve. From this understand of neurology the new approach at diagnoses, diseases, medicine that’s once only helped some will hopefully help all. There is a new discovery of a mechanism that controls the way nerve cells in the brain respond with each other to maintain our learning and long-term memory could have major benefits to understanding how the brain works and what goes wrong in neurodegenerative disorders. The findings will have a strong impact on many aspects of neuroscience. As neurology continues to improve, there are many treatments and cures waiting to be

Before leaving the nucleus the pre-mRNA may go through a process called RNA splicing (Brooker). During this process the undesirable introns are disposed of while the coding sequences, exons, are spliced together to form messenger RNA (Brooker). Understanding RNA splicing, the most important process that may alter a protein’s shape is alternative splicing (Brooker). This process allows one strand of pre-messenger RNA to produce several different polypeptide sequences (Brooker). One pre-mRNA can create multiple polypeptide sequences which in turn creates proteins that are distinctive from each other. Alternative splicing is seen in the LMNA gene, it produces Lamins A and C (Swahari). Although they are different proteins, they are believed to be functionally redundant (Swahari). During the formation of these proteins a farnesyl group, which embeds into the cell membrane, is added to one end and later the protein is cleaved at a recognition site in exon 11 removing the tip and the farnesyl group (Swahari). Due to the point mutation linked to HGPS 50 amino acids are removed, within these is the recognition site (Swahari). As a result the protein is permanently farnesylated and known as progerin (Swahari). This protein imbeds and accumulates in the cell membrane creating the symptoms of HGPS (Swahari).

Histone modifications have a very crucial role when it comes to silencing genes through chromatin remodeling. Changes in histone modifications can highly disrupt neuronal functions, along with inhibitions to the gene, BDNF (Brain-derived neurotrophic factor), which is crucial for cognition, learning, memory formation, and vulnerability to social life and experiences. Mutations in this gene are associated with susceptibility to Schizophrenia. Increased inhibition of this gene has a positive correlation with methylated CpG sites. Currently, anti-depressants keep receptors active. I will try to develop a method that would perhaps uninhibit the down-regulation of BDNF.

Which functions in transcription of rRNA by interacting with upstream binding factor (UBF), an RNA polymerase I present within the nucleolus (Dauwerse et al., 2010). It was acknowledged that Tcof1 is expressed throughout the neuroepithelium strongly where its role is crucial for cell survival (Dixon et al., 1996), which was supported by an earlier study that demonstrated Tcof1 +/- haploinsufficient mouse models developed Treacher Collin’s syndrome due to widespread apoptosis of neuroepithelial cells, defective synthesis and proliferation of neural crest cells and deficiencies in ribosome biogenesis (Valdez et al.,

Regulation of Kifs in the tri-synaptic circuitry during LTM. Preliminary analysis of expression of 30 kinesins in RNAs isolated from microdissected24 CA1, CA3 and dentate gyrus (DG) neurons of the adult mouse after one hour of CFC training suggest sub-region specific upregulation of kinesins (Fig 1M,N,O). This exciting finding suggests that specific kinesins are recruited for transport related to learning in sub-regions of the tri-synaptic circuitry. The objective of this aim is to determine the necessity and sufficiency of the transcriptional change in kinesins in CA1, CA3 and DG neurons for storing contextual fear memories. This systematic characterization of the transcriptional changes in kinesin in tri-synaptic circuitry will provide novel insights into pre and postsynaptic regulation of specific kinesins and significance of kinesin-mediated upregulation in specific neuronal circuits for storing

The exon junction complex (EJC) is a well-known RBP: an RNP complex consists of at least four core proteins (eIF4AIII, BTZ, MAGOH, and RBM8a). EJC factors labels the exon junctions of mRNA and plays critical roles in mRNA splicing, export and degradation. Recent studies revealed that recessive mutations of RBM8a cause thrombocytopenia-absent-radius (TAR) syndrome, a disease characterized by low platelet count and absence of upper limb and often with congenital heart/kidney defects, and intellectual disability (ID). Moreover, RBM8a is located in the chromosome 1q21.1 region, which is associated with ID, autism, schizophrenia and microcephaly. Given the importance of RBM8a, surprisingly little is known about its physiological functions in memory formation and its roles in human diseases. Thus, there is a critical need to elucidate the underlying molecular processes modulated by RBM8a. Lack of such knowledge, treatment options for patients carrying similar risk alleles are unlikely to improve

BDNF is a member of the neurotrophin family, which includes nerve growth factor, neurotrophin-3, neurotrophin-4/5, and neurotrophin-6 (Poo, 2001). BDNF is broadly expressed in the developing and adult mammalian brain (Poo, 2001), as well as in several peripheral tissues, such as the muscle (Cassiman et al., 2001) and adipose tissue (Sornelli et al., 2009). BDNF plays an important role in various aspects of developmental and adult brain plasticity, including proliferation, differentiation, and survival of neurons, neurogenesis, synaptic plasticity, and cognitive function (Monteggia et al., 2004).

In an animal cell, plasma membrane is the border surrounding the cell that allows the passage of enough oxygen, nutrients, and wastes (98). Cytoplasm is region between the cell membrane and the nucleus, and that is where we find various types of organelles of specific form and their tasks (98). The nucleus is an information center that contains most of the genetic information (DNA) and it controls the activities by creating messenger RNA (mRNA) so it can instruct protein synthesis (102). The nucleus’s outer layer is surrounded by nuclear envelope, which is a double membrane (inner and outer membrane (102). Furthermore, the nuclear envelope has pores that allow proteins, RNAs, etc. to enter or exit the nucleus (102). In other words, it is like a gate that controls passage area between the nucleus and cytoplasm. Moreover, within the nucleus there is another organelle called nucleolus where the ribosomal RNA (rRNA) is synthesized (102). Ribosomes are complexes that are made of rRNA and proteins inside of nucleolus (102-103). They help synthesize proteins, meaning that it helps create proteins in a cell. There are two types of ribosomes: free ribosomes and bound ribosomes. Most of the proteins are made by free ribosomes that functions within the cytoplasm (102). Whereas bound ribosomes are attached to the endoplasmic reticulum in order to make proteins that will go into the membrane, sent within certain organelles, or export of the cell (102-104). There are two types of

BDNF is a neurotrophic factor that has demonstrated neural regeneration, reconnection, and improved synaptic efficacy.23