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Lost in Translation

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Science's STKE  16 May 2006:
Vol. 2006, Issue 335, pp. tw166
DOI: 10.1126/stke.3352006tw166

Dyskeratosis congenita (DC) is a rare inherited disorder associated with bone marrow failure, skin defects, and an increased susceptibility to cancer. The X-linked form, X-DC, is caused by mutations in the DKC1 gene, which encodes a pseudouridine synthase that modifies ribosomal RNA. Yoon et al. show that disruption of DKC1 impairs translation of a select group of messenger RNAs (mRNAs) that initiate protein synthesis in an unusual way, through internal ribosome entry site (IRES) elements. Among the mRNAs affected were those encoding the tumor suppressor p27kip1 and two proteins that prevent cell death, Bcl-xL and XIAP (for X-linked inhibitor of apoptosis protein). Loss of these protein functions may contribute to the pathogenesis of X-DC.

A. Yoon, G. Peng, Y. Brandenburg, O. Zollo, W. Xu, E. Rego, D. Ruggero, Impaired control of IRES-mediated translation in X-linked dyskeratosis congenita. Science 312, 902-906 (2006). [Abstract] [Full Text]