Manipulation of Leukocytes Using Therapeutic RNAi Delivered by Targeted and Stabilized Nanoparticles - Nanotechnology for the Delivery of Therapeutic Nucleic Acids - page 180

8.1 Introduction

RNAi is a natural cellular mechanism for regulating gene expression
that is conserved in a wide range of organisms [1]. This regulation
is mediated by dsRNA, which silences the expression of the gene
bearing the complementary nucleotide sequences, either by
degrading the specific mRNA or by blocking the translation of the
mRNA (Fig. 8.1). RNAi is activated by endogenous non-coding RNAs
designated microRNAs (miRNAs), which are transcribed initially as
pri-miRNA. These long hairpin-structured transcripts are processed
by RNase III Drosha into 70 to 100 pre-miRNAs, which are then

Cytoplasm

Cytoplasm

Nucleus

Nucleus

pri-miRNA

pri-miRNA

P

Drosha Drosha

P

siRNA /
antagomir

siRNA/
miRNA mimetic/
antagomir

miRNA mimetic

pri-miRNA pre-miRNA

P

P

Dicer

Dicer

P P

pri-miRNA

pre-miRNA

P P

Mature miRNA

Mature miRNA

RISC/miRISC RISC/miRISC

Guide strand Guide strand

mRNA

mRNA

Transition inhibition

mRNA degradataion

mRNA degradation Transition inhibition

Figure 8.1 The RNAi mechanism for regulating gene expression.