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Cytoskeletal protein filamin A is a nucleolar protein that suppresses ribosomal RNA gene transcription

Deng, Wensheng, Lopez-Camacho, Cesar, Tang, Jen-Yang, Mendoza-Villanueva, Daniel, Maya-Mendoza, Apolinar, Jackson, Dean A. and Shore, Paul 2012. Cytoskeletal protein filamin A is a nucleolar protein that suppresses ribosomal RNA gene transcription. Proceedings of the National Academy of Sciences of the United States of America 109 (5) , pp. 1524-1529. 10.1073/pnas.1107879109

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH426 Genetics
Publisher: National Academy of Sciences
ISSN: 0027-8424
Last Modified: 19 Mar 2016 23:17
URI: http://orca-mwe.cf.ac.uk/id/eprint/45665

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