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POSTAR3: an updated platform for exploring post-transcriptional regulation coordinated by RNA-binding proteins.

ABSTRACT: RNA-binding proteins (RBPs) play key roles in post-transcriptional regulation. Accurate identification of RBP binding sites in multiple cell lines and tissue types from diverse species is a fundamental endeavor towards understanding the regulatory mechanisms of RBPs under both physiological and pathological conditions. Our POSTAR annotation processes make use of publicly available large-scale CLIP-seq datasets and external functional genomic annotations to generate a comprehensive map of RBP binding sites and their association with other regulatory events as well as functional variants. Here, we present POSTAR3, an updated database with improvements in data collection, annotation infrastructure, and analysis that support the annotation of post-transcriptional regulation in multiple species including: we made a comprehensive update on the CLIP-seq and Ribo-seq datasets which cover more biological conditions, technologies, and species; we added RNA secondary structure profiling for RBP binding sites; we provided miRNA-mediated degradation events validated by degradome-seq; we included RBP binding sites at circRNA junction regions; we expanded the annotation of RBP binding sites, particularly using updated genomic variants and mutations associated with diseases. POSTAR3 is freely available at http://postar.ncrnalab.org.

SUBMITTER: Zhao W

PROVIDER: S-EPMC8728292 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

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POSTAR3: an updated platform for exploring post-transcriptional regulation coordinated by RNA-binding proteins.

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