Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins
Abstract Background A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges t...
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doaj-7bd753fbac7546c7ad4fb5a7375a17e92020-11-25T02:10:47ZengBMCGenome Biology1474-760X2020-04-0121112610.1186/s13059-020-01982-9Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteinsEric L. Van Nostrand0Gabriel A. Pratt1Brian A. Yee2Emily C. Wheeler3Steven M. Blue4Jasmine Mueller5Samuel S. Park6Keri E. Garcia7Chelsea Gelboin-Burkhart8Thai B. Nguyen9Ines Rabano10Rebecca Stanton11Balaji Sundararaman12Ruth Wang13Xiang-Dong Fu14Brenton R. Graveley15Gene W. Yeo16Department of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoDepartment of Cellular and Molecular Medicine, University of California San DiegoDepartment of Genetics and Genome Sciences, Institute for Systems Genomics, UConn HealthDepartment of Cellular and Molecular Medicine, University of California San DiegoAbstract Background A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale analysis across datasets. The development of enhanced CLIP (eCLIP) enabled the mapping of targets for 150 RBPs in K562 and HepG2, creating a unique resource of RBP interactomes profiled with a standardized methodology in the same cell types. Results Our analysis of 223 eCLIP datasets reveals a range of binding modalities, including highly resolved positioning around splicing signals and mRNA untranslated regions that associate with distinct RBP functions. Quantification of enrichment for repetitive and abundant multicopy elements reveals 70% of RBPs have enrichment for non-mRNA element classes, enables identification of novel ribosomal RNA processing factors and sites, and suggests that association with retrotransposable elements reflects multiple RBP mechanisms of action. Analysis of spliceosomal RBPs indicates that eCLIP resolves AQR association after intronic lariat formation, enabling identification of branch points with single-nucleotide resolution, and provides genome-wide validation for a branch point-based scanning model for 3′ splice site recognition. Finally, we show that eCLIP peak co-occurrences across RBPs enable the discovery of novel co-interacting RBPs. Conclusions This work reveals novel insights into RNA biology by integrated analysis of eCLIP profiling of 150 RBPs with distinct functions. Further, our quantification of both mRNA and other element association will enable further research to identify novel roles of RBPs in regulating RNA processing.http://link.springer.com/article/10.1186/s13059-020-01982-9eCLIPCLIP-seqRNA binding proteinRNA processing |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eric L. Van Nostrand Gabriel A. Pratt Brian A. Yee Emily C. Wheeler Steven M. Blue Jasmine Mueller Samuel S. Park Keri E. Garcia Chelsea Gelboin-Burkhart Thai B. Nguyen Ines Rabano Rebecca Stanton Balaji Sundararaman Ruth Wang Xiang-Dong Fu Brenton R. Graveley Gene W. Yeo |
spellingShingle |
Eric L. Van Nostrand Gabriel A. Pratt Brian A. Yee Emily C. Wheeler Steven M. Blue Jasmine Mueller Samuel S. Park Keri E. Garcia Chelsea Gelboin-Burkhart Thai B. Nguyen Ines Rabano Rebecca Stanton Balaji Sundararaman Ruth Wang Xiang-Dong Fu Brenton R. Graveley Gene W. Yeo Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins Genome Biology eCLIP CLIP-seq RNA binding protein RNA processing |
author_facet |
Eric L. Van Nostrand Gabriel A. Pratt Brian A. Yee Emily C. Wheeler Steven M. Blue Jasmine Mueller Samuel S. Park Keri E. Garcia Chelsea Gelboin-Burkhart Thai B. Nguyen Ines Rabano Rebecca Stanton Balaji Sundararaman Ruth Wang Xiang-Dong Fu Brenton R. Graveley Gene W. Yeo |
author_sort |
Eric L. Van Nostrand |
title |
Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins |
title_short |
Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins |
title_full |
Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins |
title_fullStr |
Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins |
title_full_unstemmed |
Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins |
title_sort |
principles of rna processing from analysis of enhanced clip maps for 150 rna binding proteins |
publisher |
BMC |
series |
Genome Biology |
issn |
1474-760X |
publishDate |
2020-04-01 |
description |
Abstract Background A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale analysis across datasets. The development of enhanced CLIP (eCLIP) enabled the mapping of targets for 150 RBPs in K562 and HepG2, creating a unique resource of RBP interactomes profiled with a standardized methodology in the same cell types. Results Our analysis of 223 eCLIP datasets reveals a range of binding modalities, including highly resolved positioning around splicing signals and mRNA untranslated regions that associate with distinct RBP functions. Quantification of enrichment for repetitive and abundant multicopy elements reveals 70% of RBPs have enrichment for non-mRNA element classes, enables identification of novel ribosomal RNA processing factors and sites, and suggests that association with retrotransposable elements reflects multiple RBP mechanisms of action. Analysis of spliceosomal RBPs indicates that eCLIP resolves AQR association after intronic lariat formation, enabling identification of branch points with single-nucleotide resolution, and provides genome-wide validation for a branch point-based scanning model for 3′ splice site recognition. Finally, we show that eCLIP peak co-occurrences across RBPs enable the discovery of novel co-interacting RBPs. Conclusions This work reveals novel insights into RNA biology by integrated analysis of eCLIP profiling of 150 RBPs with distinct functions. Further, our quantification of both mRNA and other element association will enable further research to identify novel roles of RBPs in regulating RNA processing. |
topic |
eCLIP CLIP-seq RNA binding protein RNA processing |
url |
http://link.springer.com/article/10.1186/s13059-020-01982-9 |
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