CstF64: cell cycle regulation and functional role in 3' end processing of replication-dependent histone mRNAs.

Romeo, Valentina; Griesbach, Esther; Schümperli, Daniel (2014). CstF64: cell cycle regulation and functional role in 3' end processing of replication-dependent histone mRNAs. Molecular and cellular biology, 34(23), pp. 4272-4284. American Society for Microbiology 10.1128/MCB.00791-14

[img] Text
CstF64.pdf - Published Version
Restricted to registered users only
Available under License Publisher holds Copyright.

Download (3MB) | Request a copy

The 3' end processing of animal replication-dependent histone mRNAs is activated during G1/S-phase transition. The processing site is recognized by stem-loop binding protein and the U7 snRNP, but cleavage additionally requires a heat-labile factor (HLF), composed of cleavage/polyadenylation specificity factor, symplekin, and cleavage stimulation factor 64 (CstF64). Although HLF has been shown to be cell cycle regulated, the mechanism of this regulation is unknown. Here we show that levels of CstF64 increase toward the S phase and its depletion affects histone RNA processing, S-phase progression, and cell proliferation. Moreover, analyses of the interactions between CstF64, symplekin, and the U7 snRNP-associated proteins FLASH and Lsm11 indicate that CstF64 is important for recruiting HLF to histone precursor mRNA (pre-mRNA)-resident proteins. Thus, CstF64 is central to the function of HLF and appears to be at least partly responsible for its cell cycle regulation. Additionally, we show that misprocessed histone transcripts generated upon CstF64 depletion mainly accumulate in the nucleus, where they are targets of the exosome machinery, while a small cytoplasmic fraction is partly associated with polysomes.

Item Type:

Journal Article (Original Article)

Division/Institute:

08 Faculty of Science > Department of Biology > Institute of Cell Biology

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Romeo, Valentina; Griesbach, Esther and Schümperli, Daniel

Subjects:

500 Science > 570 Life sciences; biology

ISSN:

0270-7306

Publisher:

American Society for Microbiology

Language:

English

Submitter:

Daniel Schümperli

Date Deposited:

11 May 2015 17:18

Last Modified:

10 Sep 2015 09:50

Publisher DOI:

10.1128/MCB.00791-14

PubMed ID:

25266659

BORIS DOI:

10.7892/boris.68847

URI:

https://boris.unibe.ch/id/eprint/68847

Actions (login required)

Edit item Edit item
Provide Feedback