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RNA Biol. 2016;13(2):128-33. doi: 10.1080/15476286.2015.1096484. Epub 2015 Oct 19.

Retention and splicing complex (RES) - the importance of cooperativity.

Author information

1
a Department for NMR-based Structural Biology ; Max Planck Institute for Biophysical Chemistry ; Am Fassberg 11, Göttingen , Germany.
2
b German Center for Neurodegenerative Diseases (DZNE) ; Göttingen , Germany.
3
c Center for Nanoscale Microscopy and Molecular Physiology of the Brain; University Medical Center ; Göttingen , Germany.

Abstract

One of the great challenges to structural biologists lies in explaining the complexities of the spliceosome - a ribosome-sized molecular machine that is assembled in a step-wise manner and is responsible for pre-mRNA splicing. The spliceosome is both fascinating and difficult to work with, because of its dynamic nature. At each discrete step of splicing tens of proteins come and go orchestrating the functional transition through massive structural rearrangements. The retention and splicing complex (RES) is an important splicing factor interacting with pre-mRNA at the onset of the first transesterification reaction. RES is a specific splicing factor for a number of genes and is important for controlling pre-mRNA retention in the nucleus. RES is a 71 kDa heterotrimer composed of the 3 proteins Pml1p, Bud13p and Snu17p. We solved the 3-dimensional structure of the core of the RES complex as well as the 2 dimers, Snu17p-Bud13p and Snu17p-Pml1p. Further biophysical analysis revealed an astounding cooperativity that governs the assembly of this trimeric complex as well as its interaction with pre-mRNA. The more than 100-fold cooperativity originates from the progressive rigidification of Snu17p upon coupled binding-and-folding of protein regions, which are disordered in the unbound state. Our work highlights the role of cooperativity in the spliceosome and poses new questions about the structure and assembly of the spliceosome.

KEYWORDS:

Cooperativity; NMR spectroscopy; spliceosome; structure

PMID:
26479714
PMCID:
PMC4829318
DOI:
10.1080/15476286.2015.1096484
[Indexed for MEDLINE]
Free PMC Article

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