Diamond Publications - Search Results

Search Again...

These results only include publications that have been reviewed and processed by Diamond Light Source. To also view papers that have not yet been processed click here.

You can use the folder icon under Actions to collate papers as required. You can then click on View Folder in the left-hand navigation to review and/or download your folder.

One item found (0 items not approved).

Instruments / Technical Area	Publication Details	Published	Actions
I03-Macromolecular Crystallography I04-Macromolecular Crystallography	Differential role for phosphorylation in alternative polyadenylation function versus nuclear import of SR-like protein CPSF6 Sooin Jang , Nicola J. Cook , Valerie Pye , Gregory J. Bedwell , Amanda M. Dudek , Parmit K. Singh , Peter Cherepanov , Alan N. Engelman Nucleic Acids Research 10 DOI: 10.1093/nar/gkz206 Diamond Proposal Number(s): [9424] Open Access Show Abstract ▼ Abstract: Cleavage factor I mammalian (CFIm) complex, composed of cleavage and polyadenylation specificity factor 5 (CPSF5) and serine/arginine-like protein CPSF6, regulates alternative polyadenylation (APA). Loss of CFIm function results in proximal polyadenylation site usage, shortening mRNA 3′ untranslated regions (UTRs). Although CPSF6 plays additional roles in human disease, its nuclear translocation mechanism remains unresolved. Two β-karyopherins, transportin (TNPO) 1 and TNPO3, can bind CPSF6 in vitro, and we demonstrate here that while the TNPO1 binding site is dispensable for CPSF6 nuclear import, the arginine/serine (RS)-like domain (RSLD) that mediates TNPO3 binding is critical. The crystal structure of the RSLD-TNPO3 complex revealed potential CPSF6 interaction residues, which were confirmed to mediate TNPO3 binding and CPSF6 nuclear import. Both binding and nuclear import were independent of RSLD phosphorylation, though a hyperphosphorylated mimetic mutant failed to bind TNPO3 and mislocalized to the cell cytoplasm. Although hypophosphorylated CPSF6 largely supported normal polyadenylation site usage, a significant number of mRNAs harbored unnaturally extended 3′ UTRs, similar to what is observed when other APA regulators, such as CFIIm component proteins, are depleted. Our results clarify the mechanism of CPSF6 nuclear import and highlight differential roles for RSLD phosphorylation in nuclear translocation versus regulation of APA.	Mar 2019

Instruments / Technical Area

Publication Details

Published

Actions

I03-Macromolecular Crystallography
I04-Macromolecular Crystallography

Differential role for phosphorylation in alternative polyadenylation function versus nuclear import of SR-like protein CPSF6

Sooin Jang , Nicola J. Cook , Valerie Pye , Gregory J. Bedwell , Amanda M. Dudek , Parmit K. Singh , Peter Cherepanov , Alan N. Engelman

Nucleic Acids Research 10

DOI: 10.1093/nar/gkz206

Diamond Proposal Number(s): [9424]