1. RNA interference in biology and disease
by Carol A. Sledz, and Bryan R. G. Williams
Blood
Volume 106(3):
August 1, 2005
©2005 by American Society of Hematology

2. RNA silencing pathways.
RNA silencing pathways. Long dsRNA and shRNA or miRNA precursors are processed to siRNA or miRNA by the double-stranded RNA binding and RNase III–like enzyme Dicer into 21 to 23 nucleotide dsRNA intermediates. These are subsequently unwound and assembled into the RNA-induced silencing complex (RISC; siRNAs), which directs RNA cleavage, or into an miRNA-effector complex termed miRNP, which directs translational repression (mRNA target identified by the 5′cap, 7 mG, and poly A tail).
Carol A. Sledz, and Bryan R. G. Williams Blood 2005;106:
©2005 by American Society of Hematology

3. PKR activation by dsRNA.
PKR activation by dsRNA. Long dsRNA, shRNA, or pre-miRNA can activate protein kinase R (PKR) via binding to the dsRNA binding motifs, causing a conformational change, dimerization, and autophosphorylation. Activated PKR can inhibit protein synthesis by phosphorylation of translational initiation factor eIF2α. PKR can also function as a signal-transducing kinase interacting with IκB kinase (IKK) and p38 mitogen-activated protein kinase (p38) regulating gene transcription by activation of different transcription factors including NFκB and ATF2.
Carol A. Sledz, and Bryan R. G. Williams Blood 2005;106:
©2005 by American Society of Hematology

4. Activation of IRF3 by siRNA.
Activation of IRF3 by siRNA. Long dsRNA, siRNA, or miRNAs can activate interferon regulatory factor 3 (IRF3) via Toll-like receptor 3 (TLR3)–dependent or –independent pathways via noncanonical kinases TBK1 or IKKe or the canonical kinase complex IKK, resulting in transcriptional up-regulation of interferons and other primary response genes.
Carol A. Sledz, and Bryan R. G. Williams Blood 2005;106:
©2005 by American Society of Hematology