Position-dependent splicing activation and repression by SR and hnRNP proteins rely on common mechanisms
Steffen Erkelenz,William F. Mueller,Melanie S. Evans,Anke Busch,Katrin Schöneweis,Klemens J. Hertel,Heiner Schaal +6 more
TLDR
It is shown that SR and hnRNP splicing factors exploit similar mechanisms to positively or negatively influence splice site selection, based on their binding location relative to regulated 5' splice sites.Abstract:
Alternative splicing is regulated by splicing factors that modulate splice site selection. In some cases, however, splicing factors show antagonistic activities by either activating or repressing splicing. Here, we show that these opposing outcomes are based on their binding location relative to regulated 59 splice sites. SR proteins enhance splicing only when they are recruited to the exon. However, they interfere with splicing by simply relocating them to the opposite intronic side of the splice site. hnRNP splicing factors display analogous opposing activities, but in a reversed position dependence. Activation by SR or hnRNP proteins increases splice site recognition at the earliest steps of exon definition, whereas splicing repression promotes the assembly of nonproductive complexes that arrest spliceosome assembly prior to splice site pairing. Thus, SR and hnRNP splicing factors exploit similar mechanisms to positively or negatively influence splice site selection.read more
Citations
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Context-dependent control of alternative splicing by RNA-binding proteins
Xiang-Dong Fu,Manuel Ares +1 more
TL;DR: Some of the emerging rules that govern the highly context-dependent and combinatorial nature of alternative splicing regulation are described.
Journal ArticleDOI
A large-scale binding and functional map of human RNA-binding proteins
Eric L. Van Nostrand,Peter Freese,Gabriel A. Pratt,Xiaofeng Wang,Xintao Wei,Rui Xiao,Rui Xiao,Steven M. Blue,Jia-Yu Chen,Neal A.L. Cody,Daniel Dominguez,Sara Olson,Balaji Sundararaman,Lijun Zhan,Cassandra Bazile,Louis Philip Benoit Bouvrette,Julie Bergalet,Michael O. Duff,Keri E. Garcia,Chelsea Gelboin-Burkhart,Myles Hochman,Nicole J. Lambert,Hairi Li,Michael P. McGurk,Thai B. Nguyen,Tsultrim Palden,Ines Rabano,Shashank Sathe,Rebecca Stanton,Amanda Su,Ruth Wang,Brian A. Yee,Bing Zhou,Ashley L. Louie,Stefan Aigner,Xiang-Dong Fu,Eric Lécuyer,Eric Lécuyer,Christopher B. Burge,Brenton R. Graveley,Gene W. Yeo +40 more
TL;DR: The spectrum of RBP binding throughout the transcriptome and the connections between these interactions and various aspects of RNA biology, including RNA stability, splicing regulation and RNA localization are described.
Journal ArticleDOI
Mechanisms and Functions of Long Non-Coding RNAs at Multiple Regulatory Levels
TL;DR: The functions and mechanisms of lncRNAs in plants, humans, and animals at different regulatory levels are summarized.
Journal ArticleDOI
Regulation of Splicing by SR proteins and SR Protein-Specific Kinases
Zhi-Hong Zhou,Xiang-Dong Fu +1 more
TL;DR: The rules for SR proteins to function as splicing regulators depend on where they bind in exon versus intronic regions, on alternative exons versus flanking competing exons, and on cooperative as well as competitive binding between different SR protein family members on many of those locations.
Journal ArticleDOI
Alternative Splicing Regulatory Networks: Functions, Mechanisms, and Evolution
TL;DR: High-throughput sequencing-based methods and their applications in the study of transcriptomes have revolutionized the understanding of alternative splicing and emphasized the need for a coordinated, community-based effort to systematically address the functions of individual splice variants associated with normal and disease biology.
References
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