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Functional characterization of long non-coding RNA transcribed from the antisense strand in the VEGFA gene locus

Grant number: 10/51152-7
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): September 01, 2010
Effective date (End): January 16, 2016
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Sergio Verjovski Almeida
Grantee:Dinar Yunusov
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):15/01397-7 - Functional characterization of TFAP2A-AS2 long non-coding RNA in human in vitro trophoblast model, BE.EP.DD


As a consequence of significant advances in knowledge about the Molecular Biology of the cell it became obvious that the latter represents a well-tuned system that is regulated on several interconnected levels and that is much more complex than expected before. Gene expression is one of the basic levels on which this regulation can be executed and the complexity of the mechanisms involves the action of different classes of functional non-protein-coding RNAs (ncRNAs). Our group is involved in functional characterization of long ncRNAs transcribed from the antisense strand of intronic regions of protein-coding genes. Generally speaking, intronic ncRNAs are postulated to act on both transcriptional (by modulating chromatin architecture or interference with the transcriptional machinery) and post-transcriptional (by regulating alternative splicing or stability of mRNA) levels. The data obtained during our previous work emphasize the possibility that ncRNAs may have important functional roles in gene expression regulation. The goal of this project is to investigate the possible mechanisms of action of the ncRNA transcript which has been detected by several high-throughput expression measurements in the literature to be transcribed from the antisense strand of the fifth intron of VEGFA, a gene encoding Vascular Endothelial Growth Factor A. This ncRNA has not yet been investigated and we expect to elucidate its expression pattern in different cell lines and its possible mechanisms of function. VEGF-A protein is implicated in normal and pathologic angiogenesis and it was shown to be significantly unregulated in many tumors. It is expressed in several isoforms that are considered to have different functions in blood vessel growth. As one of various possible mechanisms of function for the above-mentioned antisense transcript (ncVEGF, non-coding VEGF) action we propose its potential influence on VEGFA pre-mRNA splicing. (AU)

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
SHERIDAN, MEGAN A.; YUNUSOV, DINAR; BALARAMAN, VELMURUGAN; ALEXENKO, ANDREI P.; YABE, SHINICHIRO; VERJOVSKI-ALMEIDA, SERGIO; SCHUST, DANNY J.; FRANZ, ALEXANDER W.; SADOVSKY, YOEL; TOSHIHIKO, EZASHI; ROBERTS, R. MICHAEL. Vulnerability of primitive human placental trophoblast to Zika virus. Proceedings of the National Academy of Sciences of the United States of America, v. 114, n. 9, p. E1587-E1596, FEB 28 2017. Web of Science Citations: 37.

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