| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print March 11, 2002
Department of Immunology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030
Corresponding Author: mwilkins{at}mail.mdanderson.org
Nonsense-mediated decay (NMD) is an RNA surveillance pathway that degrades mRNAs containing premature termination codons (PTC). T-cell receptor (TCR) and immunoglobulin (Ig) transcripts, which are encoded by genes that very frequently acquire PTCs during lymphoid ontogeny, are downregulated much more dramatically in response to PTCs than are other known transcripts. Another feature unique to TCR, Ig, and a subset of other mRNAs is that they are downregulated in response to nonsense codons in the nuclear fraction of cells. This is paradoxical, as the only well-recognized entity that can recognize nonsense codons is the cytoplasmic translation apparatus. Therefore, we investigated whether translation is responsible for this nuclear-associated mechanism. We found that the downregulation of TCR-beta transcripts in response to nonsense codons requires several features of translation, including an initiator AUG and the ability to scan. We also found that optimal downregulation depends on a Kozak consensus sequence surrounding the initiator AUG and that it can be initiated by an internal ribosome entry site (IRES), neither of which has been demonstrated before for any other PTC-bearing mRNA. At least a portion of this downregulatory response is mediated by the NMD pathway, as anti-sense hUPF2 transcripts increased the levels of PTC-bearing TCR-beta transcripts in the nuclear fraction of cells. We conclude that a hUPF2-dependent RNA surveillance pathway with translation-like features operating in the nuclear fraction of cells prevents the expression of potentially deleterious truncated proteins encoded by non-productively rearranged TCR genes.
J. Biol. Chem, 10.1074/jbc.M111781200
Submitted on December 10, 2001
Revised on February 5, 2002
Accepted on March 11, 2002
A quality-control pathway that downregulates aberrant TCR transcripts by a mechanism requiring UPF2 and translation
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Huntzinger, I. Kashima, M. Fauser, J. Sauliere, and E. Izaurralde SMG6 is the catalytic endonuclease that cleaves mRNAs containing nonsense codons in metazoan RNA, December 1, 2008; 14(12): 2609 - 2617. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Weischenfeldt, I. Damgaard, D. Bryder, K. Theilgaard-Monch, L. A. Thoren, F. C. Nielsen, S. E. W. Jacobsen, C. Nerlov, and B. T. Porse NMD is essential for hematopoietic stem and progenitor cells and for eliminating by-products of programmed DNA rearrangements Genes & Dev., May 15, 2008; 22(10): 1381 - 1396. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Barbier, M. Dutertre, D. Bittencourt, G. Sanchez, L. Gratadou, P. de la Grange, and D. Auboeuf Regulation of H-ras Splice Variant Expression by Cross Talk between the p53 and Nonsense-Mediated mRNA Decay Pathways Mol. Cell. Biol., October 15, 2007; 27(20): 7315 - 7333. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-F. Chang, W.-K. Chan, J. S. Imam, and M. F. Wilkinson Alternatively Spliced T-cell Receptor Transcripts Are Up-regulated in Response to Disruption of Either Splicing Elements or Reading Frame J. Biol. Chem., October 12, 2007; 282(41): 29738 - 29747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wittmann, E. M. Hol, and H.-M. Jack hUPF2 Silencing Identifies Physiologic Substrates of Mammalian Nonsense-Mediated mRNA Decay Mol. Cell. Biol., February 15, 2006; 26(4): 1272 - 1287. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. WACHTEL, B. LI, J. SPERLING, and R. SPERLING Stop codon-mediated suppression of splicing is a novel nuclear scanning mechanism not affected by elements of protein synthesis and NMD RNA, November 18, 2004; 10(11): 1740 - 1750. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Salati, W. Szeszel-Fedorowicz, H. Tao, M. A. Gibson, B. Amir-Ahmady, L. P. Stabile, and D. L. Hodge Nutritional Regulation of mRNA Processing J. Nutr., September 1, 2004; 134(9): 2437S - 2443S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Ferraiuolo, C.-S. Lee, L. W. Ler, J. L. Hsu, M. Costa-Mattioli, M.-J. Luo, R. Reed, and N. Sonenberg A nuclear translation-like factor eIF4AIII is recruited to the mRNA during splicing and functions in nonsense-mediated decay PNAS, March 23, 2004; 101(12): 4118 - 4123. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Bateman, S. Freddi, G. Nattrass, and R. Savarirayan Tissue-specific RNA surveillance? Nonsense-mediated mRNA decay causes collagen X haploinsufficiency in Schmid metaphyseal chondrodysplasia cartilage Hum. Mol. Genet., February 1, 2003; 12(3): 217 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. NATHANSON, T. XIA, and M. P. DEUTSCHER Nuclear protein synthesis: A re-evaluation RNA, January 1, 2003; 9(1): 9 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Mendell, C. M. J. ap Rhys, and H. C. Dietz Separable Roles for rent1/hUpf1 in Altered Splicing and Decay of Nonsense Transcripts Science, October 11, 2002; 298(5592): 419 - 422. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Tao, W. Szeszel-Fedorowicz, B. Amir-Ahmady, M. A. Gibson, L. P. Stabile, and L. M. Salati Inhibition of the Splicing of Glucose-6-phosphate Dehydrogenase Precursor mRNA by Polyunsaturated Fatty Acids J. Biol. Chem., August 16, 2002; 277(34): 31270 - 31278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, J. I. Hamilton, M. S. Carter, S. Li, and M. F. Wilkinson Alternatively Spliced TCR mRNA Induced by Disruption of Reading Frame Science, July 5, 2002; 297(5578): 108 - 110. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
