USP15 regulates dynamic protein-protein interactions of the spliceosome through deubiquitination of PRP31.

Abstract:

:Post-translational modifications contribute to the spliceosome dynamics by facilitating the physical rearrangements of the spliceosome. Here, we report USP15, a deubiquitinating enzyme, as a regulator of protein-protein interactions for the spliceosome dynamics. We show that PRP31, a component of U4 snRNP, is modified with K63-linked ubiquitin chains by the PRP19 complex and deubiquitinated by USP15 and its substrate targeting factor SART3. USP15SART3 makes a complex with USP4 and this ternary complex serves as a platform to deubiquitinate PRP31 and PRP3. The ubiquitination and deubiquitination status of PRP31 regulates its interaction with the U5 snRNP component PRP8, which is required for the efficient splicing of chromosome segregation related genes, probably by stabilizing the U4/U6.U5 tri-snRNP complex. Collectively, our data suggest that USP15 plays a key role in the regulation of dynamic protein-protein interactions of the spliceosome.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Das T,Park JK,Park J,Kim E,Rape M,Kim EE,Song EJ

doi

10.1093/nar/gkw1365

subject

Has Abstract

pub_date

2017-05-05 00:00:00

pages

4866-4880

issue

8

eissn

0305-1048

issn

1362-4962

pii

gkw1365

journal_volume

45

pub_type

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