Cytoskeletal protein filamin A is a nucleolar protein that suppresses ribosomal RNA gene transcription.
Filamin A (FLNA) is an actin-binding protein with a well-established role in the cytoskeleton, where it determines cell shape and locomotion by cross-linking actin filaments. Mutations in FLNA are associated with a wide range of genetic disorders. Here we demonstrate a unique role for FLNA as a nucleolar protein that associates with the RNA polymerase I (Pol I) transcription machinery to suppress rRNA gene transcription. We show that depletion of FLNA by siRNAs increased rRNA expression, rDNA promoter activity and cell proliferation. Immunodepletion of FLNA from nuclear extracts resulted in a decrease in rDNA promoter-driven transcription in vitro. FLNA coimmunoprecipitated with the Pol I components actin, TIF-IA, and RPA40, and their occupancy of the rDNA promoter was increased in the absence of FLNA in vivo. The FLNA actin-binding domain is essential for the suppression of rRNA expression and for inhibiting recruitment of the Pol I machinery to the rDNA promoter. These findings reveal an additional role for FLNA as a regulator of rRNA gene expression and have important implications for our understanding of the role of FLNA in human disease.
Faculty of Life Sciences,  University of Manchester, Manchester M13 9PT,  United Kingdom.
Wensheng
W
Deng
Cesar
C
Lopez-Camacho
Jen-Yang
JY
Tang
Daniel
D
Mendoza-Villanueva
Apolinar
A
Maya-Mendoza
Dean A
DA
Jackson
Paul
P
Shore
D000199:Actins; D001665:Binding Sites; D002460:Cell Line; D003285:Contractile Proteins / Q000378:metabolism / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism / Q000502:physiology*; D004275:DNA, Ribosomal / Q000235:genetics; D064448:Filamins; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism / Q000502:physiology*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012335:RNA, Ribosomal / Q000235:genetics*; D034741:RNA, Small Interfering; D014158:Transcription, Genetic / Q000502:physiology*
D000199:Actins; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; D004275:DNA, Ribosomal; D064448:Filamins; D008840:Microfilament Proteins; D012335:RNA, Ribosomal; D034741:RNA, Small Interfering