Molecular Biology

Noncanonical function of a splicing factor

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Science  05 Apr 2019:
Vol. 364, Issue 6435, pp. 39-40
DOI: 10.1126/science.364.6435.39-g

Mutations in messenger RNA (mRNA) splicing factors are found in cancer, but whether and how these mutations contribute to tumorigenesis are not clear. Palangat et al. show that a mutant splicing factor contributes to tumor progression by affecting protein translation instead of misregulating splicing. The splicing factor U2AF1 directly binds selective mRNAs near the start codon, leading to translation repression. A recurrent oncogenic mutation in U2AF1, Ser34 Phe, decreases affinity with mRNAs and behaves dominant-negatively to affect translation of hundreds of mRNAs. One of the significantly increased proteins is the inflammatory cytokine interleukin-8, which contributes to cancer progression in a cell-nonautonomous fashion.

Genes Dev. 10.1101/gad.319590.118 (2019).

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