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| Status |
Public on Mar 12, 2021 |
| Title |
miRNA-independent function of long noncoding pri-miRNA loci |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Among the large, diverse set of mammalian long noncoding RNAs (lncRNAs), long noncoding primary microRNAs (lnc-pri-miRNAs) are those that host miRNAs. Whether lnc-pri-miRNA loci have important biological function independent of their cognate miRNAs is poorly understood. From a genome-scale lncRNA screen, lnc-pri-miRNA loci were enriched for function in cell proliferation, and in glioblastoma (i.e., GBM) cells with DGCR8 or DROSHA knockdown, lnc-pri-miRNA screen hits still regulated cell growth. To molecularly dissect the function of a lnc-pri-miRNA locus, we studied LOC646329 (also known as MIR29HG), which hosts the miR-29a/b1 cluster. In GBM cells, LOC646329 knockdown reduced miR-29a/b1 levels, and these cells exhibited decreased growth. However, genetic deletion of the miR-29a/b1 cluster (LOC646329-miR29Δ) did not decrease cell growth, while knockdown of LOC646329-miR29Δ transcripts reduced cell proliferation. The miR-29a/b1-independent activity of LOC646329 corresponded to enhancer-like activation of a neighboring oncogene (MKLN1), regulating cell propagation. The LOC646329 locus interacts with the MKLN1 promoter, and antisense oligonucleotide knockdown of the lncRNA disrupts these interactions and reduces the enhancer-like activity. More broadly, analysis of genome-wide data from multiple human cell types showed that lnc-pri-miRNA loci are significantly enriched for DNA looping interactions with gene promoters as well as genomic and epigenetic characteristics of transcriptional enhancers. Functional studies of additional lnc-pri-miRNA loci demonstrated cognate miRNA-independent enhancer-like activity. Together, these data demonstrate that lnc-pri-miRNA loci can regulate cell biology via both miRNA-dependent and miRNA-independent mechanisms.
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| Overall design |
Analysis of transcriptome following knockdown of LOC646329 in different genotypes
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| Contributor(s) |
He D, Wu D, Lim DA |
| Citation(s) |
33758101 |
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| Submission date |
Sep 06, 2019 |
| Last update date |
Jun 11, 2021 |
| Contact name |
David Wu |
| Organization name |
UCSF
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| Lab |
Dan Lim
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| Street address |
35 Medical Center Way
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| City |
San Francisco |
| State/province |
California |
| ZIP/Postal code |
94143 |
| Country |
USA |
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| Platforms (2) |
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| Samples (39)
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| Relations |
| BioProject |
PRJNA564324 |
| SRA |
SRP220725 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE137048_counts.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
| GSE137048_counts_GSM4504755-GSM4504766.tsv.gz |
8.0 Kb |
(ftp)(http) |
TSV |
| GSE137048_h3k9me3_counts.tsv.gz |
497.5 Kb |
(ftp)(http) |
TSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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