RNA Activation: A Diamond in the Rough for Genome Engineers

Abstract

The ability to develop efficient and versatile technologies for manipulating gene expression is a fundamental issue both in biotechnology and therapeutics. The endogenous RNA interference (RNAi) pathway which mediates gene silencing was discovered at the end of the 20th century and it is nowadays considered as an essential strategy for knockdown of specific genes and for studying gene function. Remarkably, during the past decade, a RNA-induced mechanism of gene activation has also been reported. Likewise RNAi, the RNA activation (RNAa) process is also mediated by sequence-specific double-stranded RNA (dsRNA) molecules, and interesting resemblances between both RNA-based transcriptional mechanisms have been described. Small activating RNAs (saRNAs) and related molecules have been used for targeting of genes in species that are as different as nematodes and humans, and similar dsRNA-induced activation phenomena have also been observed in plants. The aim of this letter is to highlight recent molecular insights into yet unexplored RNAa mechanism and its potential for manipulating transcriptional activity.

Emerging Therapeutic Approaches for Diamond Blackfan Anemia

“…The RITA complex recognizes complementary sequences on the promoter of the target gene and induces histone modification and transcription initiation [95]. The modulation of transcriptional activity by saRNAs might be employed not only to study gene function but also for therapeutic applications in various diseases [96, 97]. No data on RNAa of ribosomal protein genes is yet available.…”

Study on chromatin regulation patterns of expression vectors in the PhiC31 integration site

“…To overcome the adverse effects of transgene silencing, it is typically necessary to incorporate regulatory elements into the expression vector that can prevent both transgene silencing and position effects, this ensures a more efficient and stable integrated expression [ 22–24 ]. Additionally, modulation of the expression vector’s promoter through the use of chromatin regulatory elements or activating RNA can further enhance expression efficiency and impede transgene silencing by modifying the chromatin structure [ 25 , 26 ]. However, it remains to be clarified whether the open chromatin region integrated by PhiC31 can be regulated by chromatin regulatory elements and RNA to further improve expression and overcome transgene silencing effects.…”

RNA activation in ticks

“…Although further studies are required to elucidate the detailed mechanism by which RNAa occurs in ticks, the outcome of this study provides new opportunities for the use of RNAa as a gene overexpression tool in future studies on tick biology, to reduce the global burden of ticks and tick-borne diseases.The manipulation of gene expression is instrumental to understanding disease mechanisms and developing novel therapeutics 1-8 . In the last decade, this technology has focused mainly on gene silencing through the process of RNA interference (RNAi), based on the primary understanding of noncoding small RNAs (ncRNAs) such as double-stranded RNAs (dsRNAs) and short interfering RNAs (siRNAs) 4,5,9 , where gene function is assessed by the suppression of the gene expression. Recent reports have revealed a new role for ncRNAs in a phenomenon known as RNA activation (RNAa) 2,10-13 .…”

“…The manipulation of gene expression is instrumental to understanding disease mechanisms and developing novel therapeutics 1-8 . In the last decade, this technology has focused mainly on gene silencing through the process of RNA interference (RNAi), based on the primary understanding of noncoding small RNAs (ncRNAs) such as double-stranded RNAs (dsRNAs) and short interfering RNAs (siRNAs) 4,5,9 , where gene function is assessed by the suppression of the gene expression. Recent reports have revealed a new role for ncRNAs in a phenomenon known as RNA activation (RNAa) 2,10-13 .…”