English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  The zinc finger domains in U2AF26 and U2AF35 have diverse functionalities including a role in controlling translation

Herdt, O., Reich, S., Medenbach, J., Timmermann, B., Olofsson, D., Preußner, M., et al. (2020). The zinc finger domains in U2AF26 and U2AF35 have diverse functionalities including a role in controlling translation. RNA Biology, 2020. doi:10.1080/15476286.2020.1732701.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/21.11116/0000-0005-FAB9-1 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-FABA-0
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Herdt, Olga, Author
Reich, Stefan, Author
Medenbach, Jan, Author
Timmermann, Bernd1, Author              
Olofsson, Didrik, Author
Preußner, Marco, Author
Heyd, Florian, Author
Affiliations:
1Sequencing (Head: Bernd Timmermann), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479670              

Content

show
hide
Free keywords: T cell activation; U2AF; protein stability; splicing; translation; zinc finger
 Abstract: Recent work has associated point mutations in both zinc fingers (ZnF) of the spliceosome component U2AF35 with malignant transformation. However, surprisingly little is known about the functionality of the U2AF35 ZnF domains in general. Here we have analysed key functionalities of the ZnF domains of mammalian U2AF35 and its paralog U2AF26. Both ZnFs are required for splicing regulation, whereas only ZnF2 controls protein stability and contributes to the interaction with U2AF65. These features are confirmed in a naturally occurring splice variant of U2AF26 lacking ZnF2, that is strongly induced upon activation of primary mouse T cells and localized in the cytoplasm. Using Ribo-Seq in a model T cell line we provide evidence for a role of U2AF26 in activating cytoplasmic steps in gene expression, notably translation. Consistently, an MS2 tethering assay shows that cytoplasmic U2AF26/35 increase translation when localized to the 5'UTR of a model mRNA. This regulation is partially dependent on ZnF1 thus providing a connection between a core splicing factor, the ZnF domains and the regulation of translation. Altogether, our work reveals unexpected functions of U2AF26/35 and their ZnF domains, thereby contributing to a better understanding of their role and regulation in mammalian cells.

Details

show
hide
Language(s): eng - English
 Dates: 2020-02-102020-03-01
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1080/15476286.2020.1732701
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: RNA Biology
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Georgetown, TX : Landes Bioscience
Pages: - Volume / Issue: 2020 Sequence Number: - Start / End Page: - Identifier: ISSN: 1547-6286
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000021460