PMID- 19383765
OWN - NLM
STAT- MEDLINE
DCOM- 20090730
LR  - 20211020
IS  - 1469-9001 (Electronic)
IS  - 1355-8382 (Print)
IS  - 1355-8382 (Linking)
VI  - 15
IP  - 6
DP  - 2009 Jun
TI  - Post-transcriptional control of DGCR8 expression by the Microprocessor.
PG  - 1005-11
LID - 10.1261/rna.1591709 [doi]
AB  - The Microprocessor, comprising the RNase III Drosha and the double-stranded RNA 
      binding protein DGCR8, is essential for microRNA (miRNA) biogenesis. In the miRNA 
      processing pathway certain hairpin structures within primary miRNA (pri-miRNA) 
      transcripts are specifically cleaved by the Microprocessor to release 
      approximately 60-70-nucleotide precursor miRNA (pre-miRNA) intermediates. 
      Although both Drosha and DGCR8 are required for Microprocessor activity, the 
      mechanisms regulating the expression of these proteins are unknown. Here we 
      report that the Microprocessor negatively regulates DGCR8 expression. Using in 
      vitro reconstitution and in vivo studies, we demonstrate that a hairpin, 
      localized in the 5' untranslated region (5'UTR) of DGCR8 mRNA, is cleaved by the 
      Microprocessor. Accordingly, knockdown of Drosha leads to an increase in DGCR8 
      mRNA and protein levels in cells. Furthermore, we found that the DGCR8 5'UTR 
      confers Microprocessor-dependent repression of a luciferase reporter gene in 
      vivo. Our results uncover a novel feedback loop that regulates DGCR8 levels.
FAU - Triboulet, Robinson
AU  - Triboulet R
FAU - Chang, Hao-Ming
AU  - Chang HM
FAU - Lapierre, Robert J
AU  - Lapierre RJ
FAU - Gregory, Richard I
AU  - Gregory RI
LA  - eng
PT  - Letter
PT  - Research Support, Non-U.S. Gov't
DEP - 20090421
PL  - United States
TA  - RNA
JT  - RNA (New York, N.Y.)
JID - 9509184
RN  - 0 (5' Untranslated Regions)
RN  - 0 (DGCR8 protein, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - EC 3.1.26.3 (DROSHA protein, human)
RN  - EC 3.1.26.3 (Ribonuclease III)
SB  - IM
MH  - 5' Untranslated Regions
MH  - Cells, Cultured
MH  - HeLa Cells
MH  - Humans
MH  - MicroRNAs/*metabolism
MH  - Proteins/*genetics/metabolism
MH  - RNA Processing, Post-Transcriptional
MH  - RNA, Messenger/*metabolism
MH  - RNA-Binding Proteins
MH  - Ribonuclease III/genetics/*metabolism
MH  - Transfection
PMC - PMC2685516
EDAT- 2009/04/23 09:00
MHDA- 2009/07/31 09:00
PMCR- 2009/12/01
CRDT- 2009/04/23 09:00
PHST- 2009/04/23 09:00 [entrez]
PHST- 2009/04/23 09:00 [pubmed]
PHST- 2009/07/31 09:00 [medline]
PHST- 2009/12/01 00:00 [pmc-release]
AID - rna.1591709 [pii]
AID - RA [pii]
AID - 10.1261/rna.1591709 [doi]
PST - ppublish
SO  - RNA. 2009 Jun;15(6):1005-11. doi: 10.1261/rna.1591709. Epub 2009 Apr 21.