Question

4) The importance of the translational molecular machinery to insert the correct amino acid into the primary structure of a polypeptide is of paramount importance to ensure the fidelity of the code. Part of the reason why this process is so accurate is due to the action of tRNA amino-acyl synthetase (ARSs) enzymes. Mutations within the genes for ARSs, are known to because of certain human maladies, such as the neurodegenerative disorder Charcot-Marie-Tooth (CMT) disease along with other central nervous system dysfunctions, and cancer. Interestingly, not all those who possess mutations within specific ARS genes do not display the disease phenotype. Provide at least one reason why a person might survive. Remember, do not just name a concept. Describe the concept and then explain WHY (on a molecular level) this explanation holds true.

Answer 1

Biological systems require substantial amounts of aminoacylated transfer RNA (tRNA) to properly decode various amino acids with appropriate and correct amino acids for the synthesis of various proteins to translate genetic information into proteins. The job of creating the aminoacylated, or the “charged,” tRNAs is carried out by a family of enzymes called aminoacyl-tRNA synthetases (aaRSs). To charge the commonly used different 20 proteinogenic amino acids onto their corresponding tRNAs, 20 members are included in the aaRS family.

In human cells, two aaRSs exist for their respective use in cytosolic and mitochondrial protein synthesis.

A total of 37 aaRS genes are encoded by the human nuclear genome, including 17 for mitochondria only, 18 for cytoplasm only, and 2 use for both sites. GlyRS and LysRS are the two dual-localized aaRSs, with their mitochondria targeting sequences included or excluded by alternative mRNA splicing or alternative sites of translation initiation. According to various scientists, the first human genetic disease associated with a mutation in aaRS was a neurodegenerative disease that has been shown to mainly affect the peripheral nervous system. It was named Charcot–Marie–Tooth disease (CMT), If we talk more about this disease, it has also been reported by Scientists as hereditary motor and sensory neuropathy, it affects the peripheral nerves in a way dependent on the length and at the same time, it affects a lot of problems. Also increases such as weakness and wasting of the distal limb muscles leading to progressive motor impairment, sensory loss, and skeletal malformations. Based on the predominant pathological features, CMT is divided into two major types: the demyelinating type 1, where abnormalities occur in the myelin sheath surrounding peripheral axons, and the axonal type 2, where the damage is within the axon itself. The many differents aaRS-linked with CMT subtypes usually present as axonal peripheral neuropathies, and sometimes the nerve conduction velocity (NCV) can be in the range associated with demyelination. The many patients has predominantly motor deficits, with maximum variable symptoms in terms of severity. Maily seen the lower limbs are mainly affected by CMT, most patients with GlyRS mutations have upper limb predominance. Despite these heterogeneities, clinical presentations of CMT patients with aaRS mutations are similar, implying shared disease mechanisms. Although the maximum disease phenotypes linked with bi-allelic aaRS mutations may sometimes include neuropathies, the CMT and the related neuropathies are mainly associated with cytoplasmic aaRSs through single-allelic mutations, including a special sensitivity and vulnerability of the peripheral nervous system toward mono-allelic aaRS mutations. It is possible that additional aaRSs may be linked; however, some characteristics that emerged from the existing list suggest a potential selectivity of certain aaRSs to be associated with CMT