U1 interference (U1i) for antiviral approaches

Advances in Experimental Medicine and Biology
Lorea Blazquez, Puri Fortes

Abstract

U1 snRNP (U1 small nuclear ribonucleoprotein) is an essential component of the splicing machinery. U1 snRNP also plays an additional role in 3'-end mRNA processing when it binds close to polyadenylation sites (PAS). Cotranscriptionally, U1 snRNP binding close to putative PAS prevents premature cleavage and polyadenylation and consequently safeguards pre-mRNA transcripts and defines promoter directionality. At the 3'-end of mRNAs, U1 snRNP binding to putative PAS may regulate mRNA length or inhibit polyadenylation and, therefore, gene expression. U1 interference (U1i) is a technique to inhibit gene expression based on the property of U1 snRNP to inhibit polyadenylation. It requires the expression of a modified U1 snRNP, which interacts with a target gene upstream of its PAS and inhibits target gene expression. U1i has been used to inhibit the expression of reporter or endogenous genes both in tissue culture and in animal models. In addition, U1i combination with RNA interference (RNAi), another RNA-based gene silencing technology, results in a synergistic increased inhibition. This is of special interest for antiviral therapy, where strong inhibitions may be required to decrease the expression of replicative viral RNAs and impac...Continue Reading

Citations

May 26, 2016·Pflügers Archiv : European journal of physiology·Anton OgorodnikovSven Danckwardt
Apr 4, 2021·Life Sciences·Mohsen SheykhhasanMassoud Saidijam

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