Research Topic

Transcription and Translation Defects in Neurocognitive and Neurobehavioral Disorders: Towards Accurate Diagnostics and Novel Therapeutics

About this Research Topic

The growth of expertise in molecular technologies and analyses of genomes, gene transcripts and proteins, have facilitated the development of greater insights into the molecular mechanisms involved in neurodevelopment, and have expanded capabilities to determine underlying molecular defects involved in the ...

The growth of expertise in molecular technologies and analyses of genomes, gene transcripts and proteins, have facilitated the development of greater insights into the molecular mechanisms involved in neurodevelopment, and have expanded capabilities to determine underlying molecular defects involved in the etiology of neurocognitive and neurobehavioral disorders.

Accurate regulation of gene transcription and protein translation are critical to brain development and to neuronal functions throughout life. A substantial proportion of genes linked to neurodevelopmental disorders encode regulators of transcription or chromatin structure. Abnormal RNA processing has a role in childhood onset neurological diseases. Alternate splicing normally leads to inclusion of micro-exons into mRNA transcripts of specific genes expressed in brain, and altered regulation of this process was reported to occur in 26.9% of brain samples from autistic individuals. 3’ end polyadenylation differences have been associated with specific diseases, including neuronal diseases. Moreover, defects in tRNA metabolism can lead to neurodevelopmental disorders, and have been associated with microcephaly and epileptic encephalopathy in children.

Improvements in discovery of underlying molecular and biochemical differences in neurocognitive and neurobehavioral defects continue to be important for patient management, genetic counseling and in development of therapeutic approaches. Application of transcriptome and functional analyses are proving increasingly useful in diagnosis of neurodevelopmental disorders that lead to neurocognitive and neurobehavioral problems. The diagnostic yield for disorders that impact the central nervous system has greatly increased with the application of exome sequencing, RNA sequencing, and functional analyses, which have the potential not only to guide diagnosis, but also to facilitate the design of treatments. However, a large percentage of cases remain undiagnosed and interpretation of pathogenicity of sequence variants remains challenging. In addition, further insights and methodologies need to be applied to investigate the possible impact of mutations in regulatory elements.

The goal of this Research Topic is to elicit reports of progress in the elucidation of molecular mechanisms related to gene transcription and translation events involved in the causation of neurodevelopmental, neurocognitive and neurobehavioral disorders, in the hope that this increased understanding will ultimately facilitate accurate diagnosis of the cause of the disorders, improve management of disabilities and facilitate design of appropriate novel therapies.

Specific themes of interest include studies on the downstream consequences of genomic variants identified in humans and that are thought to be related to causation of neurodevelopmental, neurocognitive, or neurobehavioral disorders. Studies of interest will include analyses of gene sequences, regulation of gene expression, impact of chromatin remodeling or modifications, information on genomic elements that act as enhancers or repressors of gene expression, analyses of transcription, translation or protein production and protein functions.

Other topics of interest may include reports on studies of any of the following:

• Functional studies on cells or tissues from individuals with neurocognitive or neurobehavioral defects who were found to have pathologic mutation on sequence analyses;

• Analyses of mRNA products derived from the gene/or genes in the regions of interest, including analysis of tissue specific mRNA splice patterns, evidence for altered polyadenylation site usage, evidence for altered transcript length and micro RNA interactions;

• tRNAs, tRNA splicing and modifications, studies on tRNA interactions with specific amino-acyl-tRNA synthases, and Interactions of tRNAs with eIF transcription initiation factors;

• Studies on ribosomes, including rates of ribosome biogenesis and ribosome sequences;

• Studies on processes involved in mRNA homeostasis, including processes involved in mRNA degradation through activity of exosomes;

• Studies on upstream signaling processes and factors that enter the nucleus and stimulate gene transcription;

• Analyses of downstream effects of putative pathogenic genomic alterations, identified in patients with neurobehavioral or neurocognitive disorders, through studies of cell lines, pluripotent stem cells or their derivatives or through introduction of putative disease- causing alterations into model organisms;

• Studies on HIV-associated neurocognitive disorders (HAND).


Professor Basson is a scientific advisor for the company Merck Sharp & Dohme. All other Topic Editors declare no competing interests.


Keywords: neurodevelopment, gene expression, translation, transcription, cognition


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Submission Deadlines

19 February 2021 Manuscript
19 March 2021 Manuscript Extension

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Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

19 February 2021 Manuscript
19 March 2021 Manuscript Extension

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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