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Series GSE188574 Query DataSets for GSE188574
Status Public on Jun 08, 2022
Title A dual-activity topoisomerase complex regulates mRNA translation and turnover
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Topoisomerase 3β (TOP3B) and TDRD3 form a dual-activity topoisomerase complex that interacts with FMRP and can change the topology of both DNA and RNA. Here, we investigated the post-transcriptional influence of TOP3B and associated proteins on mRNA translation and turnover. First, we discovered that in human HCT116 colon cancer cells, knock-out (KO) of TOP3B had similar effects on mRNA turnover and translation as did TDRD3-KO, while FMRP-KO resulted in rather distinct effects, indicating that TOP3B had stronger coordination with TDRD3 than FMRP in mRNA regulation. Second, we identified TOP3B-bound mRNAs in HCT116 cells; we found that while TOP3B did not directly influence the stability or translation of most TOP3B target mRNAs, it stabilized a subset of target mRNAs but had a more complex effect on translation--enhancing for some mRNAs whereas reducing for others. Interestingly, a point mutation that specifically disrupted TOP3B catalytic activity only partially recapitulated the effects of TOP3B-KO on mRNA stability and translation, suggesting that the impact of TOP3B on target mRNAs is only in part linked to its ability to change topology of mRNAs. Collectively, our data suggest that TOP3B-TDRD3 can regulate mRNA translation and turnover by mechanisms that are dependent and independent of topoisomerase activity.
Overall design To identify the functions of the TOP3B-TDRD3 complex on post-transcriptional regulation in HCT116 cells, total 62 samples were uploaded, including PRO-seq, RNA-seq, Ribo-seq and eCLIP-seq samples from WT and KO/KI cells. Most of them contain two or three replications. For TOP3B eCLIP-seq, TOP3B-KO cells were used as negative controls separately. For PRO-seq, RNA-seq and Ribo-seq, wild type cells were used as controls.
Contributor(s) Su S, Xue Y, Sharov A, Zhang Y, Lee SK, Martindale JL, Li W, Ku WL, Zhao K, De S, Shen W, Sen P, Gorospe M, Xu D, Wang W
Citation(s) 35748872
Submission date Nov 10, 2021
Last update date Jul 14, 2022
Contact name Weidong Wang
Organization name Shuaikun Su
Department National Institute on Aging
Lab Laboratory of Genetics and Genomics
Street address 251 Bayview Blvd
City Baltimore
State/province MD
ZIP/Postal code 21224
Country USA
Platforms (3)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (62)
GSM5685744 set24.WT.1.RNA-seq.rep1
GSM5685745 set24.WT.1.RNA-seq.rep2
GSM5685746 set20.WT.1.RNA-seq.rep3
BioProject PRJNA779461
SRA SRP345494

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Supplementary file Size Download File type/resource
GSE188574_RAW.tar 250.8 Mb (http)(custom) TAR (of BEDGRAPH)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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