SCLIP - An integrated platform to study RNA-protein interactome(s) in biomedical research: identification of CSTF2tau in alternative processing of small nuclear RNAs
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE92997 | GEO | 2017/03/01
SECONDARY ACCESSION(S): PRJNA359316
REPOSITORIES: GEO
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Project description:RNA-binding proteins (RBPs) are central for gene expression by controlling the RNA fate from birth to decay. Various disorders arising from perturbations of RNA-protein interactions document their critical function. However, deciphering their function is complex, limiting the general functional elucidation of this growing class of proteins and their contribution to (patho)physiology. Here we present sCLIP, a simplified and robust platform for genome-wide interrogation of RNA-protein interactomes based on crosslinking-immunoprecipitation and high-throughput sequencing. sCLIP exploits linear amplification of the immunoprecipitated RNA improving the complexity of the sequencing-library despite significantly reducing the amount of input material and omitting several purification steps. Additionally it permits a radiolabel-free visualization of immunoprecipitated RNA. In a proof of concept, we identify that CSTF2tau binds many previously not recognized RNAs including histone, snoRNA and snRNAs. CSTF2tau-binding is associated with internal oligoadenylation resulting in shortened snRNA isoforms subjected to rapid degradation. We provide evidence for a new mechanism whereby CSTF2tau controls the abundance of snRNAs resulting in alternative splicing of several RNAs including ANK2 with critical roles in tumorigenesis and cardiac function. Combined with a bioinformatic pipeline sCLIP thus uncovers new functions for established RBPs and fosters the illumination of RNA-protein interaction landscapes in health and disease.
2017-03-01 | GSE92996 | GEO
Project description:RNA-binding proteins (RBPs) are central for gene expression by controlling the RNA fate from birth to decay. Various disorders arising from perturbations of RNA-protein interactions document their critical function. However, deciphering their function is complex, limiting the general functional elucidation of this growing class of proteins and their contribution to (patho)physiology. Here we present sCLIP, a simplified and robust platform for genome-wide interrogation of RNA-protein interactomes based on crosslinking-immunoprecipitation and high-throughput sequencing. sCLIP exploits linear amplification of the immunoprecipitated RNA improving the complexity of the sequencing-library despite significantly reducing the amount of input material and omitting several purification steps. Additionally it permits a radiolabel-free visualization of immunoprecipitated RNA. In a proof of concept, we identify that CSTF2tau binds many previously not recognized RNAs including histone, snoRNA and snRNAs. CSTF2tau-binding is associated with internal oligoadenylation resulting in shortened snRNA isoforms subjected to rapid degradation. We provide evidence for a new mechanism whereby CSTF2tau controls the abundance of snRNAs resulting in alternative splicing of several RNAs including ANK2 with critical roles in tumorigenesis and cardiac function. Combined with a bioinformatic pipeline sCLIP thus uncovers new functions for established RBPs and fosters the illumination of RNA-protein interaction landscapes in health and disease.
2017-03-01 | GSE92995 | GEO
Project description:RNA-binding proteins (RBPs) are central for gene expression by controlling the RNA fate from birth to decay. Various disorders arising from perturbations of RNA-protein interactions document their critical function. However, deciphering their function is complex, limiting the general functional elucidation of this growing class of proteins and their contribution to (patho)physiology. Here, we present sCLIP, a simplified and robust platform for genome-wide interrogation of RNA-protein interactomes based on crosslinking-immunoprecipitation and high-throughput sequencing. sCLIP exploits linear amplification of the immunoprecipitated RNA improving the complexity of the sequencing-library despite significantly reducing the amount of input material and omitting several purification steps. Additionally, it permits a radiolabel-free visualization of immunoprecipitated RNA. In a proof of concept, we identify that CSTF2tau binds many previously not recognized RNAs including histone, snoRNA and snRNAs. CSTF2tau-binding is associated with internal oligoadenylation resulting in shortened snRNA isoforms subjected to rapid degradation. We provide evidence for a new mechanism whereby CSTF2tau controls the abundance of snRNAs resulting in alternative splicing of several RNAs including ANK2 with critical roles in tumorigenesis and cardiac function. Combined with a bioinformatic pipeline sCLIP thus uncovers new functions for established RBPs and fosters the illumination of RBP-protein interaction landscapes in health and disease.
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Project description:sCLIP - An integrated platform to study RNA-protein interactome(s) in biomedical research: identification of CSTF2tau in alternative processing of small nuclear RNAs
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Project description:The development of biomedical science requires the creation of biological material collections that allow for the search and discovery of biomarkers for pathological conditions, the identification of new therapeutic targets, and the validation of these findings in samples from patients and healthy people. Over the past decades, the importance and need for biobanks have increased considerably. Large national and international biorepositories have replaced small collections of biological samples. The aim of this work is to provide a basic understanding of biobanks and an overview of how biobanks have become essential structures in modern biomedical research.
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Project description:BackgroundNatural language processing (NLP) tools can facilitate the extraction of biomedical concepts from unstructured free texts, such as research articles or clinical notes. The NLP software tools CLAMP, cTAKES, and MetaMap are among the most widely used tools to extract biomedical concept entities. However, their performance in extracting disease-specific terminology from literature has not been compared extensively, especially for complex neuropsychiatric disorders with a diverse set of phenotypic and clinical manifestations.MethodsWe comparatively evaluated these NLP tools using autism spectrum disorder (ASD) as a case study. We collected 827 ASD-related terms based on previous literature as the benchmark list for performance evaluation. Then, we applied CLAMP, cTAKES, and MetaMap on 544 full-text articles and 20,408 abstracts from PubMed to extract ASD-related terms. We evaluated the predictive performance using precision, recall, and F1 score.ResultsWe found that CLAMP has the best performance in terms of F1 score followed by cTAKES and then MetaMap. Our results show that CLAMP has much higher precision than cTAKES and MetaMap, while cTAKES and MetaMap have higher recall than CLAMP.ConclusionThe analysis protocols used in this study can be applied to other neuropsychiatric or neurodevelopmental disorders that lack well-defined terminology sets to describe their phenotypic presentations.
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Project description:The evolution of new genes can ensue through either gene duplication and the neofunctionalization of one of the copies or the formation of a de novo gene from hitherto nonfunctional, neutrally evolving intergenic or intronic genomic sequences. Only very rarely are entire genes created de novo. Mostly, nonfunctional sequences are coopted as novel parts of existing genes, such as in the process of exonization whereby introns become exons through changes in splicing. Here, we report a case in which a novel nonprotein coding RNA evolved by intron-sequence recruitment into its structure. cDNAs derived from rat brain small RNAs, revealed a novel small nucleolar RNA (snoRNA) originating from one of the Snord115 copies in the rat Prader-Willi syndrome locus. We suggest that a single-point substitution in the Snord115 region led to the expression of a longer snoRNA variant, designated as L-Snord115. Cell culture and footprinting experiments confirmed that a single nucleotide substitution at Snord115 position 67 destabilized the kink-turn motif within the canonical snoRNA, while distal intronic sequences provided an alternate D-box region. The exapted sequence displays putative base pairing to 28S rRNA and mRNA targets.
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Project description:BackgroundWorking together efficiently and effectively presents a significant challenge in large-scale, complex, interdisciplinary research projects. Collaboratories are a nascent method to help meet this challenge. However, formal collaboratories in biomedical research centers are the exception rather than the rule.ObjectiveThe main purpose of this paper is to compare and describe two collaboratories that used off-the-shelf tools and relatively modest resources to support the scientific activity of two biomedical research centers. The two centers were the Great Lakes Regional Center for AIDS Research (HIV/AIDS Center) and the New York University Oral Cancer Research for Adolescent and Adult Health Promotion Center (Oral Cancer Center).MethodsIn each collaboratory, we used semistructured interviews, surveys, and contextual inquiry to assess user needs and define the technology requirements. We evaluated and selected commercial software applications by comparing their feature sets with requirements and then pilot-testing the applications. Local and remote support staff cooperated in the implementation and end user training for the collaborative tools. Collaboratory staff evaluated each implementation by analyzing utilization data, administering user surveys, and functioning as participant observers.ResultsThe HIV/AIDS Center primarily required real-time interaction for developing projects and attracting new participants to the center; the Oral Cancer Center, on the other hand, mainly needed tools to support distributed and asynchronous work in small research groups. The HIV/AIDS Center's collaboratory included a center-wide website that also served as the launch point for collaboratory applications, such as NetMeeting, Timbuktu Conference, PlaceWare Auditorium, and iVisit. The collaboratory of the Oral Cancer Center used Groove and Genesys Web conferencing. The HIV/AIDS Center was successful in attracting new scientists to HIV/AIDS research, and members used the collaboratory for developing and implementing new research studies. The Oral Cancer Center successfully supported highly distributed and asynchronous research, and the collaboratory facilitated real-time interaction for analyzing data and preparing publications.ConclusionsThe two collaboratory implementations demonstrated the feasibility of supporting biomedical research centers using off-the-shelf commercial tools, but they also identified several barriers to successful collaboration. These barriers included computing platform incompatibilities, network infrastructure complexity, variable availability of local versus remote IT support, low computer and collaborative software literacy, and insufficient maturity of available collaborative software. Factors enabling collaboratory use included collaboration incentives through funding mechanism, a collaborative versus competitive relationship of researchers, leadership by example, and tools well matched to tasks and technical progress. Integrating electronic collaborative tools into routine scientific practice can be successful but requires further research on the technical, social, and behavioral factors influencing the adoption and use of collaboratories.
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