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| Status |
Public on May 11, 2015 |
| Title |
A biogenesis step upstream of Microprocessor controls miR-17~92 expression |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Non-coding RNA profiling by high throughput sequencing
|
| Summary |
The precise control of miR-17~92 microRNA (miRNA) is essential for normal development and overexpression of certain miRNAs from this cluster is oncogenic. Here we find the relative expression of the six miRNAs processed from the primary (pri-miR-17~92) transcript is dynamically regulated during embryonic stem cell differentiation. We identify a new miRNA biogenesis intermediate, termed ‘progenitor-miRNA’ (pro-miRNA), that is an efficient substrate for Microprocessor. An autoinhibitory 5’ RNA fragment is cleaved to generate pro-miRNA and selectively license Microprocessor-mediated production of pre-miR-17, -18a, -19a, 20a, and -19b. Using genetic, biochemical, and structural methods we define two complementary cis-regulatory repression domains required for the formation of this inhibitory RNA conformation. We find the endonuclease CPSF3 (CPSF73), and the Spliceosome-associated ISY1 are required for pro-miRNA biogenesis and expression of all miRNAs within the cluster except miR-92. Thus, developmentally regulated generation of pro-miRNA explains the posttranscriptional control of miR-17~92 expression in development.
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| |
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| Overall design |
Illumina RNAseq in WT, dgcr8-/- and dicer-/- mESCs and small RNA seq in WT mESCs
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| |
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| Contributor(s) |
Du P, Gregory R |
| Citation(s) |
26255770 |
| |
| Submission date |
May 08, 2015 |
| Last update date |
Apr 03, 2024 |
| Contact name |
Peng Du |
| E-mail(s) |
Peng.Du@childrens.harvard.edu
|
| Organization name |
Boston Children’s Hospital, Harvard Medical School
|
| Lab |
Richard Gregory
|
| Street address |
1 Blackfan Circle
|
| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02115 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL16417 |
Illumina MiSeq (Mus musculus) |
|
| Samples (4)
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| Relations |
| BioProject |
PRJNA283413 |
| SRA |
SRP058145 |
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