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Series GSE148755 Query DataSets for GSE148755
Status Public on Aug 21, 2020
Title Integrator restrains paraspeckles assembly by promoting isoform switching of the lncRNA NEAT1
Organism Homo sapiens
Experiment type Other
Summary Alternative RNA 3’-end processing provides an important source of transcriptome diversification, which impacts various biological processes and the etiology of diseases, including cancer. A prime example of this is the transcript isoform switch that leads to the read-through expression of the long non-coding RNA NEAT1_2, at the expense of the shorter polyadenylated transcript NEAT1_1. Expression of NEAT1_2 is required for the formation of paraspeckles (PS), nuclear bodies that protect cancer cells from oncogene-induced replication stress and chemotherapy. Searching for proteins that modulate this isoform switching event we identified factors involved in the 3’-end processing of polyadenylated (pA+) RNA as well as several components of the Integrator complex. Perturbation experiments established that, by promoting the cleavage of NEAT1_2, Integrator forces NEAT1_2 to NEAT1_1 isoform switching and, thereby, restrains PS assembly. Consistently, low expression levels of several Integrator subunits correlated with poorer prognosis of cancer patients exposed to chemotherapeutics. Our study identifies Integrator as a key regulator of PS biogenesis and establish a link between Integrator, cancer biology and chemosensitivity, which may be exploited therapeutically.
Overall design enhanced UV crosslinking and immunoprecipitation (eCLIP) is a method for identifying protein binding sites to RNA. INTS11 is the catalytic subunit of the Integrator complex. eCLIP followed by high-throughput sequencing of INTS11 in HeLa cells. Two different antibodies of INTS11 (ab75276, HPA029025), size-matched input and IgG controls in duplicates
Contributor(s) Barra J, Gaidosh GS, Blumenthal E, Beckedorff F, Tayari MM, Kirstein N, Karakach TK, Jensen TH, Impens F, Gevaert K, Leucci E, Shiekhattar R, Marine J
Citation(s) 32923585
Submission date Apr 15, 2020
Last update date May 03, 2022
Contact name Felipe Beckedorff
Organization name University of Miami
Street address 1501 NW 10th Avenue room 731.G , Miami, FL
City Miami
State/province FL
ZIP/Postal code 33136
Country USA
Platforms (1)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (6)
GSM4478386 eclip_hela_ints11_sigma_IP_r1
GSM4478387 eclip_hela_ints11_abcam_IP_r2
GSM4478388 eclip_hela_ints11_sigma_input_r1
BioProject PRJNA625577
SRA SRP256512

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Supplementary file Size Download File type/resource
GSE148755_RAW.tar 132.3 Mb (http)(custom) TAR (of BED, BW)
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Raw data are available in SRA
Processed data provided as supplementary file

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