Cockayne syndrome protein A is a transcription factor of RNA polymerase I and stimulates ribosomal biogenesis and growth.
Mutations in the Cockayne syndrome A (CSA) protein account for 20% of Cockayne syndrome (CS) cases, a childhood disorder of premature aging and early death. Hitherto, CSA has exclusively been described as DNA repair factor of the transcription-coupled branch of nucleotide excision repair. Here we show a novel function of CSA as transcription factor of RNA polymerase I in the nucleolus. Knockdown of CSA reduces pre-rRNA synthesis by RNA polymerase I. CSA associates with RNA polymerase I and the active fraction of the rDNA and stimulates re-initiation of rDNA transcription by recruiting the Cockayne syndrome proteins TFIIH and CSB. Moreover, compared with CSA deficient parental CS cells, CSA transfected CS cells reveal significantly more rRNA with induced growth and enhanced global translation. A previously unknown global dysregulation of ribosomal biogenesis most likely contributes to the reduced growth and premature aging of CS patients.
Department of Dermatology and Allergic Diseases; University of Ulm; Ulm, Germany.
Sylvia
S
Koch
Department of Dermatology and Allergic Diseases; University of Ulm; Ulm, Germany.
Omar
O
Garcia Gonzalez
Department of Dermatology and Allergic Diseases; University of Ulm; Ulm, Germany.
Robin
R
Assfalg
Department of Dermatology and Allergic Diseases; University of Ulm; Ulm, Germany.
Adrian
A
Schelling
Department of Dermatology and Allergic Diseases; University of Ulm; Ulm, Germany.
Patrick
P
Schäfer
Department of Dermatology and Allergic Diseases; University of Ulm; Ulm, Germany.
Karin
K
Scharffetter-Kochanek
Department of Dermatology and Allergic Diseases; University of Ulm; Ulm, Germany.
Sebastian
S
Iben
D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism; D003057:Cockayne Syndrome / Q000235:genetics / Q000378:metabolism; D004265:DNA Helicases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism*; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D000075223:Poly-ADP-Ribose Binding Proteins; D012318:RNA Polymerase I / Q000235:genetics / Q000378:metabolism*; D012322:RNA Precursors / Q000096:biosynthesis / Q000378:metabolism; D012335:RNA, Ribosomal / Q000096:biosynthesis / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism*; D051758:Transcription Factor TFIIH / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D004275:DNA, Ribosomal; C095472:ERCC8 protein, human; D000075223:Poly-ADP-Ribose Binding Proteins; D012322:RNA Precursors; D012335:RNA, Ribosomal; D014157:Transcription Factors; D051758:Transcription Factor TFIIH; D012318:RNA Polymerase I; D004265:DNA Helicases; C078673:ERCC6 protein, human; D045643:DNA Repair Enzymes
Cockayne syndrome; DNA repair; RNA polymerase I transcription; growth; premature aging; ribosomopathy