PMID- 12944397
OWN - NLM
STAT- MEDLINE
DCOM- 20040203
LR  - 20220309
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 47
DP  - 2003 Nov 21
TI  - RNAi-mediated HuR depletion leads to the inhibition of muscle cell 
      differentiation.
PG  - 47119-28
AB  - The formation of muscle fibers involves the sequential expression of many 
      proteins that regulate key steps during myoblast-to-myotube transition. MyoD, 
      myogenin, and the cyclin-dependent kinase inhibitor p21cip1 are major players in 
      the initiation and maintenance of the differentiated state of mouse embryonic 
      muscle cells (C2C12). The messenger RNAs encoding these three proteins contain 
      typical AU-rich elements (AREs) in their 3'-untranslated regions (3'-UTRs), which 
      are known to affect the half-life of many short-lived mRNAs. HuR, an RNA-binding 
      protein that regulates both the stability and cellular movement of ARE-containing 
      mRNAs, interacts and stabilizes the p21cip1 message under UV stress in human RKO 
      colorectal carcinoma cells. Here, by the use of gel shift experiments and 
      immunoprecipitation followed by reverse transcription-PCR analysis, we show that 
      HuR interacts with MyoD, myogenin, and p21cip1 mRNAs through specific sequences 
      in their 3'-UTRs. To demonstrate the implication of endogenous HuR in myogenesis, 
      we knocked down its expression in myoblasts using RNA interference and observed a 
      significant reduction of HuR expression, associated with complete inhibition of 
      myogenesis. Moreover, the expression of MyoD and myogenin mRNAs, as well as 
      proteins, is significantly reduced in the HuR knockdown C2C12 cells. We were able 
      to completely re-establish the myogenic process of these defective cells by 
      introducing back HuR protein conjugated to a cell-permeable peptide. Finally, HuR 
      accumulates in the cytoplasm during myogenesis. Thus, our results clearly 
      demonstrated that endogenous HuR plays a crucial role in muscle differentiation 
      by regulating the expression and/or the nuclear export of ARE-containing mRNAs 
      that are essential for this process.
FAU - van der Giessen, Kate
AU  - van der Giessen K
AD  - Department of Biochemistry, McGill University, MacIOntyre Building, 3655 
      Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada.
FAU - Di-Marco, Sergio
AU  - Di-Marco S
FAU - Clair, Eveline
AU  - Clair E
FAU - Gallouzi, Imed Eddine
AU  - Gallouzi IE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030827
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (3' Untranslated Regions)
RN  - 0 (Antigens, Surface)
RN  - 0 (Cdkn1a protein, mouse)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Cyclins)
RN  - 0 (ELAV Proteins)
RN  - 0 (ELAV-Like Protein 1)
RN  - 0 (ELAVL1 protein, human)
RN  - 0 (MyoD Protein)
RN  - 0 (Myog protein, mouse)
RN  - 0 (Myogenin)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
SB  - IM
MH  - 3' Untranslated Regions/metabolism
MH  - Animals
MH  - *Antigens, Surface
MH  - Cell Differentiation/genetics
MH  - Cell Line
MH  - Cyclin-Dependent Kinase Inhibitor p21
MH  - Cyclins/genetics
MH  - ELAV Proteins
MH  - ELAV-Like Protein 1
MH  - Mice
MH  - Muscle Cells/*cytology
MH  - Muscle Development/genetics
MH  - MyoD Protein/genetics
MH  - Myogenin/genetics
MH  - Protein Binding
MH  - RNA Interference/*physiology
MH  - RNA, Messenger/metabolism
MH  - RNA-Binding Proteins/genetics/metabolism/*physiology
EDAT- 2003/08/29 05:00
MHDA- 2004/02/05 05:00
CRDT- 2003/08/29 05:00
PHST- 2003/08/29 05:00 [pubmed]
PHST- 2004/02/05 05:00 [medline]
PHST- 2003/08/29 05:00 [entrez]
AID - S0021-9258(20)76003-5 [pii]
AID - 10.1074/jbc.M308889200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 Nov 21;278(47):47119-28. doi: 10.1074/jbc.M308889200. Epub 2003 
      Aug 27.