The flightless I protein interacts with RNA-binding proteins and is involved in the genome-wide mRNA post-transcriptional regulation in lung carcinoma cells

Wang,Cuihua; Chen,Kezhi; Liao,Shengyou; Gu,Wei; Lian,Xinlei; Zhang,Jing; Gao,Xuejuan; Liu,Xiaohui; Wang,Tong; He,Qing-Yu; Zhang,Gong; Liu,Langxia

doi:10.3892/ijo.2017.3995

The flightless I protein interacts with RNA-binding proteins and is involved in the genome-wide mRNA post-transcriptional regulation in lung carcinoma cells

Authors:
- Cuihua Wang
- Kezhi Chen
- Shengyou Liao
- Wei Gu
- Xinlei Lian
- Jing Zhang
- Xuejuan Gao
- Xiaohui Liu
- Tong Wang
- Qing-Yu He
- Gong Zhang
- Langxia Liu
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Affiliations: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, Jinan University, Guangzhou, Guangdong 510632, P.R. China
Published online on: May 11, 2017 https://doi.org/10.3892/ijo.2017.3995
Pages: 347-361

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Abstract

The flightless I protein (FLII) belongs to the gelsolin family. Its function has been associated with actin remodeling, embryonic development, wound repair, and more recently with cancer. The structure of FLII is characterized by the N-terminal leucine-rich repeats (LRR) and C-terminal gesolin related repeated units that are both protein-protein interaction domains, suggesting that FLII may exert its function by interaction with other proteins. Therefore, systematic study of protein interactions of FLII in cells is important for the understanding of FLII functions. In this study, we found that FLII was downregulated in lung carcinoma cell lines H1299 and A549 as compared with normal HBE (human bronchial epithelial) cell line. The investigation of FLII interactome in H1299 cells revealed that 74 of the total 132 putative FLII interactors are involved in RNA post-transcriptional modification and trafficking. Furthermore, by using high-throughput transcriptome and translatome sequencing combined with cell fractionation, we showed that the overexpression or knockdown of FLII impacts on the overall nuclear export, and translation of mRNAs. IPA analysis revealed that the majority of these target mRNAs encode the proteins whose functions are reminiscent of those previously reported for FLII, suggesting that the post-transcriptional regulation of mRNA might be a major mechanism of action for FLII.

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