Nucleic Acids Research, 2002, Vol. 30, No. 13 2851-2861
© 2002 Oxford University Press
Internal ribosome entry site-mediated translation of Smad5 in vivo: requirement for a nuclear event
Institute for Biomolecular Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan and 1 Laboratory of Genome Structure Analysis, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan
Smad5 is thought to relay signals of the bone morphogenetic protein pathway. The 5' untranslated region (5'UTR) of human Smad5 mRNA is long, has the potential to form secondary structures and contains five AUG codons. Here we show that the 5'UTR of Smad5 contains an internal ribosome entry site (IRES) located within 100 nt of the 3' end of the 5'UTR. The Smad5 IRES was 4–8-fold more active than the poliovirus IRES in C2C12 cells, which have osteoblastic differentiation ability, but was 5–10-fold less active than the poliovirus IRES in 293T cells. When an in vitro transcript of a dicistronic Smad5 IRES construct was transfected into C2C12 cells, the Smad5 IRES was not able to stimulate the translation of the downstream cistron, although the cap-dependent translation of the upstream cistron was efficient. In contrast, the poliovirus IRES in a dicistronic in vitro transcript was able to stimulate the translation of the downstream cistron to a similar extent as in the case of transfection of the corresponding dicistronic DNA construct. These results suggest that Smad5 IRES activity displays cell specificity and that some as yet unidentified nuclear event may be required for efficient Smad5 IRES-driven translation initiation.
* To whom correspondence should be addressed. Tel: +81 3 5449 5486; Fax: +81 3 5449 5216; Email:ssugano{at}ims.u-tokyo.ac.jp Present address:Kazuko Shiroki and Kin-ichiro Miura, Proteios Research Inc., 1111 Tebiro, Kamakura City, Kanagawa 248-8555, Japan
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. D. Baird, M. Turcotte, R. G. Korneluk, and M. Holcik Searching for IRES RNA, October 1, 2006; 12(10): 1755 - 1785. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. W.-L. Li, J. Li, S. L. Timmerman, L. A. Krushel, and S. L. Martin The dicistronic RNA from the mouse LINE-1 retrotransposon contains an internal ribosome entry site upstream of each ORF: implications for retrotransposition Nucleic Acids Res., February 6, 2006; 34(3): 853 - 864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. JIMENEZ, G. M. JANG, B. L. SEMLER, and M. L. WATERMAN An internal ribosome entry site mediates translation of lymphoid enhancer factor-1 RNA, September 1, 2005; 11(9): 1385 - 1399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Bonnal, F. Pileur, C. Orsini, F. Parker, F. Pujol, A.-C. Prats, and S. Vagner Heterogeneous Nuclear Ribonucleoprotein A1 Is a Novel Internal Ribosome Entry Site trans-Acting Factor That Modulates Alternative Initiation of Translation of the Fibroblast Growth Factor 2 mRNA J. Biol. Chem., February 11, 2005; 280(6): 4144 - 4153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Hasselblatt, B. Hockenjos, C. Thoma, H. E. Blum, and W.-B. Offensperger Translation of stable hepadnaviral mRNA cleavage fragments induced by the action of phosphorothioate-modified antisense oligodeoxynucleotides Nucleic Acids Res., January 7, 2005; 33(1): 114 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. De Pietri Tonelli, M. Mihailovich, R. Schnurbus, G. Pesole, F. Grohovaz, and D. Zacchetti Translational control of Scamper expression via a cell-specific internal ribosome entry site Nucleic Acids Res., May 15, 2003; 31(10): 2508 - 2513. [Abstract] [Full Text] [PDF]
|
|