Splicing Activation by Rbfox Requires Self-Aggregation through Its Tyrosine-Rich Domain

Ying, Yi ; Wang, Xiao-Jun ; et al.

In: Cell, Jg. 170 (2017-07-01), Heft 2

academicJournal - 312 - 323.e10

Proteins of the Rbfox family act with a complex of proteins called the Large Assembly of Splicing Regulators (LASR). We find that Rbfox interacts with LASR via its C-terminal domain (CTD), and this domain is essential for its splicing activity. In addition to LASR recruitment, a low-complexity (LC) sequence within the CTD contains repeated tyrosines that mediate higher-order assembly of Rbfox/LASR and are required for splicing activation by Rbfox. This sequence spontaneously aggregates in solution to form fibrous structures and hydrogels, suggesting an assembly similar to the insoluble cellular inclusions formed by FUS and other proteins in neurologic disease. Unlike the pathological aggregates, we find that assembly of the Rbfox CTD plays an essential role in its normal splicing function. Rather than simple recruitment of individual regulators to a target exon, alternative splicing choices also depend on the higher-order assembly of these regulators within the nucleus.

Titel:	Splicing Activation by Rbfox Requires Self-Aggregation through Its Tyrosine-Rich Domain
Autor/in / Beteiligte Person:	Ying, Yi ; Wang, Xiao-Jun ; Vuong, Celine K ; Lin, Chia-Ho ; Damianov, Andrey ; Black, Douglas L
Link:	https://escholarship.org/uc/item/12383085
Zeitschrift:	Cell, Jg. 170 (2017-07-01), Heft 2
Veröffentlichung:	eScholarship, University of California, 2017
Medientyp:	academicJournal
Umfang:	312 - 323.e10
Schlagwort:	Biochemistry and Cell Biology Biological Sciences Genetics Underpinning research 1.1 Normal biological development and functioning Aetiology 2.1 Biological and endogenous factors Generic health relevance Amino Acid Sequence Animals Brain Cytoskeletal Proteins Humans Mice Protein Domains RNA Splicing RNA Splicing Factors Sequence Alignment Serine-Arginine Splicing Factors RNA-binding protein alternative splicing phase separation posttranscriptional gene regulation protein aggregate protein-protein interactions Medical and Health Sciences Developmental Biology Biological sciences Biomedical and clinical sciences
Sonstiges:	Nachgewiesen in: eScholarship Document Type: article File Description: application/pdf Rights: public

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