The maturation, stability, and subcellular localization of mRNA are determined by various RNA binding proteins (RBPs) in post-transcriptional regulation, including capping, RNA splicing, RNA editing/modification, and miRNA-induced gene silencing. Once exported out of the nucleus, mRNAs are processed in the cytoplasm or endoplasmic reticulum to synthesize specific polypeptides, which later fold into active proteins. Therefore, the error-prone protein translation processes need timely and precise regulation through the protein quality control (PQC) mechanism to maintain normal cellular functions. So far, increasing evidence shows that the dysregulation of the post-transcriptional regulation or the PQC pathway plays essential roles in the pathogenesis of numerous neurological disorders. For example, the post-transcriptional modification of RNA adenosine (m6A and m1A) affects almost all critical events during RNA processing and regulates the expression of many neurological disease genes. In addition, long non-coding RNA (lncRNA) and circular RNA (circRNA) can contribute to the pathogenesis of neurological disorders via the miRNA-induced gene silencing pathway. Moreover, the impaired PQC pathway, such as mutations of valosin-containing protein (VCP), can lead to the failure to eliminate the aggregated RBPs (FUS and TDP43), which are neurotoxic and could contribute to the pathogenesis of amyotrophic lateral sclerosis.
This Research Topic aims to gain a broader perspective on understanding the roles of post-transcriptional regulation and PQC in neurological disorders. First, we will present the functional studies of novel regulators in post-transcriptional regulation and PQC or explore the context-dependently roles of the known regulators in different clinical conditions, brain cell types, or developmental stages. Second, some regulators (e.g., argonaut, AGO) have been reported to control both miRNA-mediated gene silencing and PQC. We wish to include studies demonstrating the other crosstalk between different pathways to gain comprehensive insights into the gene regulatory network. Third, studies using novel models, such as non-human primates/pigs or patient-derived iPSCs (including specific cell types and organoids), that overcome the limitations of classic rodent models are encouraged. Fourth, we want to collect clinical evidence (e.g., genome-wide studies) or animal therapeutic studies (e.g., CRISPR/Cas13-based RNA editing or antisense oligonucleotides treatment) to better understand the importance of post-transcriptional regulation and PQC in neurological disorders.
Original Research and Review articles are encouraged on this topic. However, we also welcome other article types that present personal insights or new methods on relevant research topics. Contributions of interest include, but are not limited to:
• Novel roles of RBPs, PQC-associated proteins, RNA modifications, and ncRNAs in neurological disorders, particularly with the evidence in specific brain cell types or animal models.
• Crosstalk between RBP- and miRNA-mediated regulation or PQC- and miRNA-mediated regulation.
• Patient-derived iPSCs-based studies of neurological disorders.
• Genome-wide identification of pathogenic variants associated with post-transcriptional regulation and protein quality control in neurological disorders.
• New technologies and insights in exploring therapeutic intervention of neurological disorders by targeting the genes involved in post-transcriptional regulation and protein quality control.
The maturation, stability, and subcellular localization of mRNA are determined by various RNA binding proteins (RBPs) in post-transcriptional regulation, including capping, RNA splicing, RNA editing/modification, and miRNA-induced gene silencing. Once exported out of the nucleus, mRNAs are processed in the cytoplasm or endoplasmic reticulum to synthesize specific polypeptides, which later fold into active proteins. Therefore, the error-prone protein translation processes need timely and precise regulation through the protein quality control (PQC) mechanism to maintain normal cellular functions. So far, increasing evidence shows that the dysregulation of the post-transcriptional regulation or the PQC pathway plays essential roles in the pathogenesis of numerous neurological disorders. For example, the post-transcriptional modification of RNA adenosine (m6A and m1A) affects almost all critical events during RNA processing and regulates the expression of many neurological disease genes. In addition, long non-coding RNA (lncRNA) and circular RNA (circRNA) can contribute to the pathogenesis of neurological disorders via the miRNA-induced gene silencing pathway. Moreover, the impaired PQC pathway, such as mutations of valosin-containing protein (VCP), can lead to the failure to eliminate the aggregated RBPs (FUS and TDP43), which are neurotoxic and could contribute to the pathogenesis of amyotrophic lateral sclerosis.
This Research Topic aims to gain a broader perspective on understanding the roles of post-transcriptional regulation and PQC in neurological disorders. First, we will present the functional studies of novel regulators in post-transcriptional regulation and PQC or explore the context-dependently roles of the known regulators in different clinical conditions, brain cell types, or developmental stages. Second, some regulators (e.g., argonaut, AGO) have been reported to control both miRNA-mediated gene silencing and PQC. We wish to include studies demonstrating the other crosstalk between different pathways to gain comprehensive insights into the gene regulatory network. Third, studies using novel models, such as non-human primates/pigs or patient-derived iPSCs (including specific cell types and organoids), that overcome the limitations of classic rodent models are encouraged. Fourth, we want to collect clinical evidence (e.g., genome-wide studies) or animal therapeutic studies (e.g., CRISPR/Cas13-based RNA editing or antisense oligonucleotides treatment) to better understand the importance of post-transcriptional regulation and PQC in neurological disorders.
Original Research and Review articles are encouraged on this topic. However, we also welcome other article types that present personal insights or new methods on relevant research topics. Contributions of interest include, but are not limited to:
• Novel roles of RBPs, PQC-associated proteins, RNA modifications, and ncRNAs in neurological disorders, particularly with the evidence in specific brain cell types or animal models.
• Crosstalk between RBP- and miRNA-mediated regulation or PQC- and miRNA-mediated regulation.
• Patient-derived iPSCs-based studies of neurological disorders.
• Genome-wide identification of pathogenic variants associated with post-transcriptional regulation and protein quality control in neurological disorders.
• New technologies and insights in exploring therapeutic intervention of neurological disorders by targeting the genes involved in post-transcriptional regulation and protein quality control.