The average eukaryotic tRNA contains 13 posttranscriptional modifications; however, their functional impact is largely unknown. Our understanding of the complex tRNA aminoacylation machinery in metazoans also remains limited. Herein, using a series of high-resolution cryo-electron microscopy (cryo-EM) structures, we provide the mechanistic basis for recognition and aminoacylation of fully-modified cellular tRNA by human lysyl-tRNA synthetase (h-LysRS).
View Article and Find Full Text PDFAminoacyl-tRNA synthetases (aaRSs) are enzymes that synthesize aminoacyl-tRNAs to facilitate translation of the genetic code. Quality control by aaRS proofreading and other mechanisms maintains translational accuracy, which promotes cellular viability. Systematic disruption of proofreading, as recently demonstrated for alanyl-tRNA synthetase (AlaRS), leads to dysregulation of the proteome and reduced viability.
View Article and Find Full Text PDFTo ensure that correct amino acids are incorporated during protein synthesis, aminoacyl-tRNA synthetases (aaRSs) use proofreading mechanisms collectively referred to as editing. Although editing is important for viability, editing-deficient aaRSs have been identified in host-dependent organisms. In Mycoplasma mobile, editing-deficient PheRS and LeuRS have been identified.
View Article and Find Full Text PDFJ Neurosci Rural Pract
January 2021
One integral step in the transition from a nucleic acid encoded-genome to functional proteins is the aminoacylation of tRNA molecules. To perform this activity, aminoacyl-tRNA synthetases (aaRSs) activate free amino acids in the cell forming an aminoacyl-adenylate before transferring the amino acid on to its cognate tRNA. These newly formed aminoacyl-tRNA (aa-tRNA) can then be used by the ribosome during mRNA decoding.
View Article and Find Full Text PDFIn the wake of the recent pandemic of Corona Virus Disease 2019 (COVID-19), with confirmed cases having crossed 750,000, health systems across the world are getting overwhelmed; making it strenuous to maintain essential health services. Several changes were implemented in our acute mental health care service using a collaborative approach to maintain a balance between preventive measures to 'flatten the curve' and to provide care to those who were in need. Mode of service delivery was changed predominantly to tele-medicine, amongst others.
View Article and Find Full Text PDFMechanisms have evolved to prevent errors in replication, transcription, and translation of genetic material, with translational errors occurring most frequently. Errors in protein synthesis can occur at two steps, during tRNA aminoacylation and ribosome decoding. Recent advances in protein mass spectrometry have indicated that previous reports of translational errors have potentially underestimated the frequency of these events, but also that the majority of translational errors occur during ribosomal decoding, suggesting that aminoacylation errors are evolutionarily less tolerated.
View Article and Find Full Text PDFThe negative symptoms have been described in association with schizophrenia since the early days of it being recognized as an entity. However, their elusive nature kept them unacknowledged until there was a revival of interest in them following the development of specific quantifying measures. Over the past three decades, there has been a tremendous surge in research on their types, measurements, status in the present classificatory system, and their implications.
View Article and Find Full Text PDFSchizophrenia is a heterogenous disorder, and has often been subtyped on the basis of family history of psychotic disorders. Compared to those without, a positive family history is associated with an earlier age of onset, greater structural brain abnormalities and poorer clinical course. Given recent emphasis on mirror neuron system (MNS) in attempting to explain psychopathology in schizophrenia; present analysis tried to tease out differences in MNS functioning between these two groups.
View Article and Find Full Text PDFVisual hallucinations are commonly present in various neurological and psychiatric conditions such as schizophrenia and other hallucinatory psychosis. Current conceptualization of hallucinations assume pattern completion model of thalamus to be responsible for the origin of this type of the perceptual abnormality and proposes that central inhibition of such circuits may treat hallucinations. We present a case of chronic hallucinatory psychosis with significantly distressing visual hallucinations, resistant to antipsychotics, which successfully responded to carbamazepine.
View Article and Find Full Text PDFClin Psychopharmacol Neurosci
December 2015
Present day health-care philosophy strongly favors an increased attention to mental health related issues. However, the lack of an adequate number of trained specialists in India in this field makes it imperative that the burden is shared by general practitioners at large. But our current medical education system may not be equipped enough to prepare them for the task.
View Article and Find Full Text PDFTourette syndrome and bipolar disorder are frequent comorbidities in pediatric age group. They provide a clinician with certain unique challenges. While on one hand the tics mask manifestation of affective symptomatology, the latter makes it difficult to elicit tics with certainty.
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