title: Cytoskeletal Filamin A Differentially Modulates RNA Polymerase III Gene Transcription in Transformed Cell Lines.
abstract: Cytoskeletal filamin A (FLNA) is an important protein involved in multiple cellular processes. Previous studies have shown that FLNA can promote or inhibit cancer growth and development; however, the mechanisms underlying these events are not fully understood. Here we show that, in both 293T and SaOS2 cells, knockdown of FLNA significantly enhanced transcription of RNA polymerase (pol) III-transcribed genes except for a subset of tRNA genes. In contrast, re-expression of FLNA in an FLNA-deficient melanoma cell line (A7) repressed transcription of all pol III-transcribed genes, suggesting that FLNA inhibits pol III transcription in a cell type-specific manner. Chromatin immunoprecipitation assays revealed that the repression of pol III gene transcription by FLNA correlates with the decreased occupancy of the RNA pol III transcription machinery at promoters. Immunofluorescence microscopy and coimmunoprecipitation assays revealed that FLNA can associate with the RNA pol III transcription machinery through its actin-binding domain within nuclei. Mechanistic analysis revealed that FLNA suppresses pol III gene transcription by confining the recruitment of the RNA pol III transcription machinery at the promoters of the genes that are sensitive to the alteration of FLNA expression. These findings not only extend the understanding of FLNA function in cells but also provide novel insights into the mechanism by which FLNA represses cell proliferation.
authors.affiliation: From the Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China and.
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.affiliation: From the Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China and.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zhao
authors.affiliation: From the Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China and.
authors.forename: Yun
authors.initials: Y
authors.lastname: Wei
authors.affiliation: From the Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China and.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: the Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom paul.shore@manchester.ac.u.
authors.forename: Paul
authors.initials: P
authors.lastname: Shore
authors.affiliation: From the Institute of Biology and Medicine, Wuhan University of Science and Technology, Wuhan, Hubei Province 430065, China and dengwensheng@wust.edu.cn.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Deng
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D064448:Filamins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012320:RNA Polymerase III / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D064448:Filamins; D012320:RNA Polymerase III
keywords: RNA polymerase III; filamin; gene expression; tRNA; transcription