Journal article

Germline heterozygous mutations in Nxf1 perturb RNA metabolism and trigger thrombocytopenia and lymphopenia in mice

Stephane Chappaz, Charity W Law, Mark R Dowling, Kirstyn T Carey, Rachael M Lane, Linh H Ngo, Vihandha O Wickramasinghe, Gordon K Smyth, Matthew E Ritchie, Benjamin T Kile



In eukaryotic cells, messenger RNA (mRNA) molecules are exported from the nucleus to the cytoplasm, where they are translated. The highly conserved protein nuclear RNA export factor1 (Nxf1) is an important mediator of this process. Although studies in yeast and in human cell lines have shed light on the biochemical mechanisms of Nxf1 function, its contribution to mammalian physiology is less clear. Several groups have identified recurrent NXF1 mutations in chronic lymphocytic leukemia (CLL), placing it alongside several RNA-metabolism factors (including SF3B1, XPO, RPS15) whose dysregulation is thought to contribute to CLL pathogenesis. We report here an allelic series of germline point muta..

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Awarded by Swiss National Science Foundation

Awarded by Australian National Health and Medical Research Council

Funding Acknowledgements

This work was supported by a Swiss National Science Foundation Fellowship for Advanced Researchers (PA00P3_139695) (S.C.), grants from the Australian National Health and Medical Research Council (1113577, 1063008, 1016647, and 1154970), and a Senior Medical Research Fellowship from the Sylvia and Charles Viertel Foundation.