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)
Matéria(s) publicada(s) na Revista Pesquisa FAPESP sobre a bolsa::
(Referências obtidas automaticamente do Web of Science e do SciELO, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores)
SHERIDAN, MEGAN A.;
ALEXENKO, ANDREI P.;
SCHUST, DANNY J.;
FRANZ, ALEXANDER W.;
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,
FEB 28 2017.
Citações Web of Science: 44.
(Referências obtidas automaticamente das Instituições de Ensino e Pesquisa do Estado de São Paulo)