Poetz et al. 2022 (PRJNA779948)

General Details

Title Ribo-Seq performed in parental or CPEB4 knock-out HeLa cells
Organism
Number of Samples 4
Release Date 2021/11/12 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP345769
ENA SRP345769
GEO GSE188692
BioProject PRJNA779948

Publication

Title
Authors Poetz F, Lebedeva S, Schott J, Lindner D, Ohler U, Stoecklin G
Journal Genome biology
Publication Date 2022 Sep 12
Abstract Cytoplasmic polyadenylation element-binding protein 4 (CPEB4) is known to associate with cytoplasmic polyadenylation elements (CPEs) located in the 3' untranslated region (UTR) of specific mRNAs and assemble an activator complex promoting the translation of target mRNAs through cytoplasmic polyadenylation. Here, we find that CPEB4 is part of an alternative repressor complex that mediates mRNA degradation by associating with the evolutionarily conserved CCR4-NOT deadenylase complex. We identify human CPEB4 as an RNA-binding protein (RBP) with enhanced association to poly(A) RNA upon inhibition of class I histone deacetylases (HDACs), a condition known to cause widespread degradation of poly(A)-containing mRNA. Photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) analysis using endogenously tagged CPEB4 in HeLa cells reveals that CPEB4 preferentially binds to the 3'UTR of immediate early gene mRNAs, at G-containing variants of the canonical U- and A-rich CPE located in close proximity to poly(A) sites. By transcriptome-wide mRNA decay measurements, we find that the strength of CPEB4 binding correlates with short mRNA half-lives and that loss of CPEB4 expression leads to the stabilization of immediate early gene mRNAs. Akin to CPEB4, we demonstrate that CPEB1 and CPEB2 also confer mRNA instability by recruitment of the CCR4-NOT complex. While CPEB4 was previously known for its ability to stimulate cytoplasmic polyadenylation, our findings establish an additional function for CPEB4 as the RNA adaptor of a repressor complex that enhances the degradation of short-lived immediate early gene mRNAs. © 2022. The Author(s).
PMC PMC9465963
PMID 36096941
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR16929291 PRJNA779948 Homo sapiens HeLa Ribo-Seq 0.0
SRR16929292 PRJNA779948 Homo sapiens HeLa Ribo-Seq 0.0
SRR16929295 PRJNA779948 Homo sapiens HeLa Ribo-Seq 0.0
SRR16929296 PRJNA779948 Homo sapiens HeLa Ribo-Seq 0.0
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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