Small interfering RNA (siRNA) biogenesis

Stable Identifier
R-HSA-426486
Type
Pathway
Species
Homo sapiens
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Small interfering RNAs (siRNAs) are 21-25 nucleotide single-stranded RNAs produced by cleavage of longer double-stranded RNAs by the enzyme DICER1 within the RISC loading complex containing DICER1, an Argonaute protein, and either TARBP2 or PRKRA (PACT). Typically the long double-stranded substrates originate from viruses or repetitive elements in the genome and the two strands of the substrate are exactly complementary.
After cleavage by DICER1 the 21-25 nucleotide double-stranded product is loaded into an Argonuate protein (humans contain 4 Argonautes) and rendered single-stranded by a mechanism that is not well characterized.
siRNA-loaded AGO2 is predominantly located at the cytosolic face of the rough endoplasmic reticulum and has also been observed in the nucleus.

Literature References
PubMed ID Title Journal Year
23511973 The rough endoplasmatic reticulum is a central nucleation site of siRNA-mediated RNA silencing

Stalder, L, Heusermann, W, Sokol, L, Trojer, D, Wirz, J, Hean, J, Fritzsche, A, Aeschimann, F, Pfanzagl, V, Basselet, P, Weiler, J, Hintersteiner, M, Morrissey, DV, Meisner-Kober, NC

EMBO J. 2013
24388755 RNAi factors are present and active in human cell nuclei

Gagnon, KT, Li, L, Chu, Y, Janowski, BA, Corey, DR

Cell Rep 2014
15741316 Perspective: machines for RNAi

Tomari, Y, Zamore, PD

Genes Dev 2005
19239886 Origins and Mechanisms of miRNAs and siRNAs

Carthew, RW, Sontheimer, EJ

Cell 2009
19165215 Biogenesis of small RNAs in animals

Kim, VN, Han, J, Siomi, MC

Nat Rev Mol Cell Biol 2009
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