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| 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
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| 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.
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| 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
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| 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 |
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| Submission date |
Apr 15, 2020 |
| Last update date |
May 03, 2022 |
| Contact name |
Felipe Beckedorff |
| E-mail(s) |
beckedorff@gmail.com
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| Organization name |
University of Miami
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| Street address |
1501 NW 10th Avenue room 731.G , Miami, FL
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| City |
Miami |
| State/province |
FL |
| ZIP/Postal code |
33136 |
| Country |
USA |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA625577 |
| SRA |
SRP256512 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE148755_RAW.tar |
132.3 Mb |
(http)(custom) |
TAR (of BED, BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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