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Genome-wide analysis reveals an inappropriate accumulation of Ser-2 phosphorylation on RNA polymerase II (RNA Pol II) near the transcription start sites of 625 genes for ALS patient cells and after small interfering RNA (siRNA) knockdown of FUS in normal fibroblasts. Furthermore, both the presence of mutant FUS protein and siRNA knockdown of wild-type FUS correlate with altered distribution of RNA Pol II within fibroblast nuclei. A loss of FUS function in orchestrating Ser-2 phosphorylation of the CTD of RNA Pol II is detectable in ALS patient\u2013derived fibroblasts expressing mutant FUS protein, even when the FUS protein remains largely nuclear. A likely explanation for this loss of function is the aggregation of FUS protein in nuclei. Thus our results suggest a specific mechanism by which mutant FUS can have biological consequences other than by the formation of cytoplasmic aggregates.<\/jats:p>","DOI":"10.1091\/mbc.e14-05-1007","type":"journal-article","created":{"date-parts":[[2014,7,10]],"date-time":"2014-07-10T03:53:26Z","timestamp":1404964406000},"page":"2571-2578","source":"Crossref","is-referenced-by-count":56,"title":["FUS is sequestered in nuclear aggregates in ALS patient fibroblasts"],"prefix":"10.1091","volume":"25","author":[{"given":"Jacob C.","family":"Schwartz","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado, Boulder, CO 80309"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine R.","family":"Podell","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Chemistry and Biochemistry and BioFrontiers Institute, University of Colorado, Boulder, CO 80309"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve S. 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