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PMID: 16690864

Yoon A et al
Science 2006 May 12;312(5775):902-6
Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita.

2 comments exist on this article.

Refuted by followup study: Normal ribosome biogenesis in patients

Rank: 1

BioMed Crit Comm 2009; 2:1343
Posted: Jan 2, 2009 CCID: 1343
Commentator: rrmari	Ave. score of this commentator: 2.3 for 73 scored comments.

The authors used mouse studies to conclude that the genetic lesion of dyskeratosis congenita (DC) caused a defect in ribosome biogenesis, confirming the finding using limited studies of patients' cells. Followup studies of cells from patients differed, however (Wong and Collins, PMID: 17015423), finding no defect in ribosome biogenesis. The latter authors noted that, due to telomere dysfunction, commercially available patients' cells used casually by some investigators would have telomere shortening and senescence, which impact ribosomes independent of the DC genetic lesion.

Necessary IRES controls were omitted

Rank: 2

BioMed Crit Comm 2009; 2:1345
Posted: Jan 2, 2009 CCID: 1345
Commentator: rrmari	Ave. score of this commentator: 2.3 for 73 scored comments.

The authors concluded that mouse cells from a transgenic model of dyskeratosis congenita were "specifically impaired in translation of IRESs" (internal ribosome entry sites). According to M Kozak (PMID: 17647274), the experiments lacked the necessary controls. For example, the putative Bcl-xL "IRES" was compared only to itself and not "to a monocistronic mRNA, or to a dicistronic mRNA lacking an IRES, nor to a discistronic mRNA containing a proven IRES, if such there is." The authors also referred to IRES activity in the XIAP and p27 mRNAs, both of which are reported as effected by the transgenic defect, and yet both of these "IRES" activities had already been refuted by other authors who attributed the activities to cryptic promoters and splicing rather than actual IRES function (PMID: 16006622, PMID: 15037781).

Key authors in this publication:

Brandenburger Y, Peng G, Rego E, Ruggero D, Xu W, Yoon A.

View Linked Comments	PMID: 16690864
Yoon A et al Science 2006 May 12;312(5775):902-6 Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita.