![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
RESEARCH PAPER
Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, UK
If the 5'-proximal AUG triplet in a mammalian mRNA is followed by a short open reading frame (sORF), a significant fraction of ribosomes resume scanning after termination of sORF translation, and reinitiate at a downstream AUG. To examine the underlying mechanism, we examined reinitiation in vitro using a series of mRNAs that differed only in the 5'-untranslated region (UTR). Efficient reinitiation was found to occur only if the eIF4F complex, or at a minimum the central one-third fragment of eIF4G, participated in the primary initiation event at the sORF initiation codon. It did not occur, however, when sORF translation was driven by the classical swine fever virus or cricket paralysis virus internal ribosome entry sites (IRESs), which do not use eIF4A, 4B, 4E, or 4G. A critical test was provided by an mRNA with an unstructured 5'-UTR, which is translated by scanning but does not absolutely need eIF4G and eIF4A: There was efficient reinitiation in a standard reticulocyte lysate, when initiation would be largely driven by eIF4F, but no reinitiation in an eIF4G-depleted lysate. These results suggest that resumption of scanning may depend on the interaction between eIF4F (or the eIF4G central domain) and the ribosome being maintained while the ribosome translates the sORF.
[Keywords: Scanning ribosome mechanism; initiation factor eIF4F; initiation factor eIF4G; cricket paralysis virus IRES; classical swine fever virus (pestivirus) IRES]
Received June 30, 2003; revised version accepted November 18, 2003.
Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.276504.
E-MAIL rjj{at}mole.bio.cam.ac.uk; FAX 44-1223-766002.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  A. L. Silva, P. Ribeiro, A. Inacio, S. A. Liebhaber, and L. Romao Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay RNA, March 1, 2008; 14(3): 563 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Treder, E. L. Pettit Kneller, E. M. Allen, Z. Wang, K. S. Browning, and W. A. Miller The 3' cap-independent translation element of Barley yellow dwarf virus binds eIF4F via the eIF4G subunit to initiate translation RNA, January 1, 2008; 14(1): 134 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. A.A. Poyry, A. Kaminski, E. J. Connell, C. S. Fraser, and R. J. Jackson The mechanism of an exceptional case of reinitiation after translation of a long ORF reveals why such events do not generally occur in mammalian mRNA translation Genes & Dev., December 1, 2007; 21(23): 3149 - 3162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Luttermann and G. Meyers A Bipartite Sequence Motif Induces Translation Reinitiation in Feline Calicivirus RNA J. Biol. Chem., March 9, 2007; 282(10): 7056 - 7065. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Silva, F. J.C. Pereira, A. Morgado, J. Kong, R. Martins, P. Faustino, S. A. Liebhaber, and L. Romao The canonical UPF1-dependent nonsense-mediated mRNA decay is inhibited in transcripts carrying a short open reading frame independent of sequence context RNA, December 1, 2006; 12(12): 2160 - 2170. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. Anderson and A. M. L. Lever Human immunodeficiency virus type 1 gag polyprotein modulates its own translation. J. Virol., November 1, 2006; 80(21): 10478 - 10486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Wiesenthal, A. Leutz, and C. F. Calkhoven A translation control reporter system (TCRS) for the analysis of translationally controlled processes in the vertebrate cell Nucleic Acids Res., February 10, 2006; 34(3): e23 - e23. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. T. Humphreys, B. J. Westman, D. I. K. Martin, and T. Preiss MicroRNAs control translation initiation by inhibiting eukaryotic initiation factor 4E/cap and poly(A) tail function PNAS, November 22, 2005; 102(47): 16961 - 16966. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. G. KOLUPAEVA, A. UNBEHAUN, I. B. LOMAKIN, C. U.T. HELLEN, and T. V. PESTOVA Binding of eukaryotic initiation factor 3 to ribosomal 40S subunits and its role in ribosomal dissociation and anti-association RNA, April 1, 2005; 11(4): 470 - 486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. David-Assael, H. Saul, V. Saul, T. Mizrachy-Dagri, I. Berezin, E. Brook, and O. Shaul Expression of AtMHX, an Arabidopsis vacuolar metal transporter, is repressed by the 5' untranslated region of its gene J. Exp. Bot., March 1, 2005; 56(413): 1039 - 1047. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-H. Kim, B.-H. Kim, A. Yahalom, D. A. Chamovitz, and A. G. von Arnim Translational Regulation via 5' mRNA Leader Sequences Revealed by Mutational Analysis of the Arabidopsis Translation Initiation Factor Subunit eIF3h PLANT CELL, December 1, 2004; 16(12): 3341 - 3356. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Shibuya, T. Nishiyama, and N. Nakashima Cell-Free Synthesis of Polypeptides Lacking an Amino-Terminal Methionine by Using a Dicistroviral Intergenic Internal Ribosome Entry Site J. Biochem., November 1, 2004; 136(5): 601 - 606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Mao, Q. Zhao, M. Daigle, M. H. Ghahremani, P. Chidiac, and P. R. Albert RGS17/RGSZ2, a Novel Regulator of Gi/o, Gz, and Gq Signaling J. Biol. Chem., June 18, 2004; 279(25): 26314 - 26322. [Abstract] [Full Text] [PDF]
|
|
