Dataset Information

RADAR: annotation and prioritization of variants in the post-transcriptional regulome of RNA-binding proteins.

ABSTRACT: RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation and disease. Their binding sites cover more of the genome than coding exons; nevertheless, most noncoding variant prioritization methods only focus on transcriptional regulation. Here, we integrate the portfolio of ENCODE-RBP experiments to develop RADAR, a variant-scoring framework. RADAR uses conservation, RNA structure, network centrality, and motifs to provide an overall impact score. Then, it further incorporates tissue-specific inputs to highlight disease-specific variants. Our results demonstrate RADAR can successfully pinpoint variants, both somatic and germline, associated with RBP-function dysregulation, which cannot be found by most current prioritization methods, for example, variants affecting splicing.

SUBMITTER: Zhang J

PROVIDER: S-EPMC7391703 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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RADAR: annotation and prioritization of variants in the post-transcriptional regulome of RNA-binding proteins.

Zhang Jing J Liu Jason J Lee Donghoon D Feng Jo-Jo JJ Lochovsky Lucas L Lou Shaoke S Rutenberg-Schoenberg Michael M Gerstein Mark M

Genome biology 20200730 1

RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation and disease. Their binding sites cover more of the genome than coding exons; nevertheless, most noncoding variant prioritization methods only focus on transcriptional regulation. Here, we integrate the portfolio of ENCODE-RBP experiments to develop RADAR, a variant-scoring framework. RADAR uses conservation, RNA structure, network centrality, and motifs to provide an overall impact score. Then, it further incorporates ...[more]

PMID: 32727537

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Project description:The human neocortex is undoubtedly considered a supreme accomplishment in mammalian evolution. It features a prenatally established six-layered structure which remains plastic to the myriad of changes throughout an organism's lifetime. A fundamental feature of neocortical evolution and development is the abundance and diversity of the progenitor cell population and their neuronal and glial progeny. These evolutionary upgrades are partially enabled due to the progenitors' higher proliferative capacity, compartmentalization of proliferative regions, and specification of neuronal temporal identities. The driving force of these processes may be explained by temporal molecular patterning, by which progenitors have intrinsic capacity to change their competence as neocortical neurogenesis proceeds. Thus, neurogenesis can be conceptualized along two timescales of progenitors' capacity to (1) self-renew or differentiate into basal progenitors (BPs) or neurons or (2) specify their fate into distinct neuronal and glial subtypes which participate in the formation of six-layers. Neocortical development then proceeds through sequential phases of proliferation, differentiation, neuronal migration, and maturation. Temporal molecular patterning, therefore, relies on the precise regulation of spatiotemporal gene expression. An extensive transcriptional regulatory network is accompanied by post-transcriptional regulation that is frequently mediated by the regulatory interplay between RNA-binding proteins (RBPs). RBPs exhibit important roles in every step of mRNA life cycle in any system, from splicing, polyadenylation, editing, transport, stability, localization, to translation (protein synthesis). Here, we underscore the importance of RBP functions at multiple time-restricted steps of early neurogenesis, starting from the cell fate transition of transcriptionally primed cortical progenitors. A particular emphasis will be placed on RBPs with mostly conserved but also divergent evolutionary functions in neural progenitors across different species. RBPs, when considered in the context of the fascinating process of neocortical development, deserve to be main protagonists in the story of the evolution and development of the neocortex.

Dataset Information

RADAR: annotation and prioritization of variants in the post-transcriptional regulome of RNA-binding proteins.

Publications

RADAR: annotation and prioritization of variants in the post-transcriptional regulome of RNA-binding proteins.

Similar Datasets

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