Embryonic lethal abnormal vision (ELAV) proteins are RNA-binding proteins that bind specific adenine and uridine-rich elements mainly located in the 3´-untranslated region of target mRNAs, preventing their otherwise rapid degradation and thus increasing gene expression. Starting from our previous discovery and applying an integrated in vitro/in silico approach, herein we report a deeper understanding of the mRNA-stabilizing activity of four peptides derived from the ELAV proteins structure. The stabilizing effect on the VEGF transcript (mRNAVEGF) exerted by each peptide, tested individually, was initially evaluated, and no effects were evidenced. Hence, the biological effects of all peptides couples were investigated. Interestingly, in accordance with preliminary molecular dynamics results, only one of all possible peptide couples resulted highly effective in stabilizing mRNAVEGF. These two peptides were thus identified as valuable starting point for designing small molecules with ELAV-mimicking properties.
Identification of Peptides with ELAV-like mRNA Stabilizing Effect: An Integrated In Vitro/In Silico Approach
AMADIO, MARIALAURA;PASCALE, ALESSIA ANGELA;GOVONI, STEFANO;GAGGERI, RAFFAELLA FRANCESCA;ROSSI, DANIELA;COLLINA, SIMONA
2013-01-01
Abstract
Embryonic lethal abnormal vision (ELAV) proteins are RNA-binding proteins that bind specific adenine and uridine-rich elements mainly located in the 3´-untranslated region of target mRNAs, preventing their otherwise rapid degradation and thus increasing gene expression. Starting from our previous discovery and applying an integrated in vitro/in silico approach, herein we report a deeper understanding of the mRNA-stabilizing activity of four peptides derived from the ELAV proteins structure. The stabilizing effect on the VEGF transcript (mRNAVEGF) exerted by each peptide, tested individually, was initially evaluated, and no effects were evidenced. Hence, the biological effects of all peptides couples were investigated. Interestingly, in accordance with preliminary molecular dynamics results, only one of all possible peptide couples resulted highly effective in stabilizing mRNAVEGF. These two peptides were thus identified as valuable starting point for designing small molecules with ELAV-mimicking properties.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
