PMID:22307607

Citation	Deng, W, Lopez-Camacho, C, Tang, JY, Mendoza-Villanueva, D, Maya-Mendoza, A, Jackson, DA and Shore, P (2012) Cytoskeletal protein filamin A is a nucleolar protein that suppresses ribosomal RNA gene transcription. Proc. Natl. Acad. Sci. U.S.A. 109:1524-9
Abstract	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.
Links	PubMed PMC3277164 Online version:10.1073/pnas.1107879109
Keywords	Actins; Binding Sites; Cell Line; Contractile Proteins/metabolism; Contractile Proteins/physiology; Cytoskeletal Proteins/metabolism; Cytoskeletal Proteins/physiology; DNA, Ribosomal/genetics; Humans; Microfilament Proteins/metabolism; Microfilament Proteins/physiology; Promoter Regions, Genetic; RNA Interference; RNA, Ribosomal/genetics; RNA, Small Interfering; Transcription, Genetic/physiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:FLNA	part_of	GO:0005730: nucleolus	ECO:0000315: mutant phenotype evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:FLNA	involved_in	GO:0016479: negative regulation of transcription by RNA polymerase I	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
HUMAN:FLNA		GO:0005730: nucleolus	ECO:0000315:		C		Figure 1 D&E	complete CACAO 5813
HUMAN:FLNA		GO:0016479: negative regulation of transcription from RNA polymerase I promoter	ECO:0000314:		P		Figure 2 demonstrates rRNA suppression by FLNA which is needed to segue into the direct assay of Figure 3. Figure 3 shows FLNA association with RNA polymerase I.	complete CACAO 5814

References

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