Introduction
RNA, also known as ribonucleic acid, is a nucleic acid in the cells of all living organisms and structurally resembles DNA (Deoxyribonucleic Acid). However, RNA is often single-stranded, like DNA. RNA serves as a messenger, carrying DNA instructions. RNA is also essential for processes like gene expression and protein synthesis. Most species use DNA as their genetic material, while some viruses use RNA. An RNA molecule has a backbone consisting of alternating phosphate groups and sugar ribose. Each sugar has one of the four bases adenine (A), uracil (U), cytosine (C), or guanine(G) attached to it. Cells contain three forms of RNA: messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA). It can perform the following functions-
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mRNA - The message is delivered through mRNA, which acts as a bridge between genes and proteins.
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tRNA - The adapter, or crucial molecule, reads the genetic information and supplies amino acids to the expanding polypeptide chain.
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rRNA - Provides a framework for protein synthesis in the ribosome and catalyzes peptide bond formation.
What Is RNA Metabolism?
RNA metabolism is the fundamental process through which RNA is produced, transported, controlled, stored, and translated. Diseases associated with abnormal RNA metabolism are an underexplored field. RNA is essential for many other catalytic and regulatory processes, including converting genetic information into proteins. Recent developments in the study of RNA metabolism have recently discovered complex processes for creating and maintaining functional RNA. RNA flaws harm cells and result in disease. Recent research has revealed that mutations in RNA-binding proteins majorly cause various human neurological disorders. This article discusses the recent discoveries of human diseases connected to flaws in RNA metabolism.
What Are Human RNA Changes and How Do They Affect Disease?
Human diseases, including cancer, cardiovascular conditions, congenital genetic disabilities, metabolic problems, neurological issues, and mitochondrial-related issues, have all been linked to mutations in around half of the already recognized RNA modification enzymes. Researchers discover that neurological disorders are significantly overrepresented among the more than 100 relationships between mutations in RNA modifying enzymes and human disease, consistent with the observed enrichment of various RNA modifications in neuronal tissues.
Pathogenic mutations, amyloid precursor proteins, superoxide dismutase, and DNA and RNA binding proteins are the main causes of these neurodegenerative disorders. In addition, age is another significant factor linked to these disorders.
What Is the Role of RNA in Neurological Diseases?
Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal degeneration (FTD), and amyotrophic lateral sclerosis (ALS), among others, are aging-related neurodegenerative diseases. These fatal neurological conditions are characterized by irreversible neuron loss and gliosis. Although the percentage of older people with dementia has decreased in developed nations, the absolute number of dementia cases is rising due to an aging population. Therefore, it is essential to understand the fundamental biological processes that lead to neurodegeneration.
RBP proteins are necessary at all levels of RNA processing in both the nucleus and the cytoplasm, including transcription, splicing, RNA stabilization, and RNA destruction. Frontotemporal degeneration (FTD) and Amyotrophic Lateral Sclerosis (ALS) represent two significant examples of RBP abnormalities (ALS). While FTD is linked to neuronal loss in the temporal and frontal cortex, ALS is a neurodegenerative disease that results in the death of upper and lower motor neurons from the motor cortex and spinal cord, respectively. TAR DNA-binding protein-43 is a nuclear RBP that connects individuals with ALS and FTD despite the varied locations of neuronal atrophy that they experience (TDP-43).
What Is the Rna Translation in Neurodegeneration?
Due to the existence of mRNA and polyribosomes, some researchers have hypothesized that the synaptic effectiveness of neuronal dendrites and dendritic spines may depend on local protein synthesis. In situ, hybridization experiments have enhanced the concept of local translation by establishing the preferential localization of particular mRNA transcripts to dendrites. According to these findings, specific RNA forms are packed into distinct ribonucleoproteins (RNPs) and transferred to the dendrites, where they are produced in a specific manner.
Local translational control affects synapses and synaptic networks. It is shown in various studies where protein synthesis inhibitors affect synaptic plasticity, including long-term potentiation (LTP), long-term depression (LTD), and long-term facilitation. Synapse-stimulating drugs have been discovered to induce protein synthesis. A type of LTP called long-lasting late-phase LTP (L-LTP) needs both gene transcription and RNA translation to occur.
The processes and interactions of the three main regulators of translation in neurons - miRNAs, fragile X mental retardation (FMRP), and cytoplasmic polyadenylation [poly(A)] element-binding (CPEB) proteins - are currently being thoroughly studied. A sequence-specific RNA-binding protein called cytoplasmic poly(A) element-binding inhibits translation until it is activated. It is triggered by signaling events and results in the elongation of mRNA's poly(A) tails, which activates translation. Cytoplasmic poly(A) complex is another related component, and it impacts the translation of mRNAs generated by poly(A) in dendrites in response to synaptic stimulation. The synaptic plasticity alterations that occur in response to the depletion of poly(A) complex components demonstrate the significance of these cytoplasmic poly (A) complexes in synaptic function. The CPEB shows a consistent post transcriptional molecular pathway.
What Is the Role of RNA in Cancer?
Breast cancer, bladder cancer, leukemia, and other cancers have all been linked to dysregulation and mutations in various RNA modification enzymes. For instance, it has been discovered that the mcm5s two modification enzymes ELP3 and CTU1/2 are up-regulated in breast cancer and support metastasis. Similar findings have been made with the overexpression of the methyltransferase NSUN2, whose expression levels have been demonstrated to link with the onset and progression of cancer. On the other hand, it has been discovered that the tRNA methyltransferase TRM9L/KIAA1456 is down-regulated in breast cancer cells and other cancer types. Together, these indicate that RNA alterations have a role in cancer. In contrast, it has not yet been established whether these enzymes could serve as potential targets for cancer treatment or biomarkers for disease prognosis.
What Is the Role of RNA in Genetic Defects?
Mutations in protein-coding genes cause the most serious genetic birth abnormalities. However, gene expression regulation can also lead to deviations from normal development. Mutations in RNA modifying enzymes have been linked to a variety of hereditary birth disorders, including the William-Beuren syndrome (WBSCR20/WBSCR22/NSUN5), the Dubowitz syndrome (NSUN2), the Noonan-like syndrome (NSUN2), and the Cri du Chat syndrome (NOP2/NOL1/p120/NSUN1). Additionally, mutations in RNA modification enzymes can lead to conditions like spina bifida (TRDMT1) and newborn death, which expose the spinal cord to the outside of the body (EMG1).
Conclusion
RNA plays an important role in a variety of bodily functions. It has significantly aided the neurological system's ability to function normally. RNA and RNP dysfunction is a major cause of many diseases, including neurodegenerative disorders. It has been suggested that RNA and associated proteins can cause these illnesses in several ways. It is crucial that preventing or redirecting pre-mRNA splicing leads to a successful restoration of activity and a decrease in RNA toxicity. It reveals that these RNAs have a larger role in these degenerative disorders.
Further research will disclose more complicated features, resulting in a greater grasp of available therapy options. A higher investment of resources in this area is required to understand the unknown domain of these human diseases. The medical community is now actively working to comprehend the complex mysteries underlying the molecular and genetic levels in them.
