Reactome | Small interfering RNA (siRNA) biogenesis

Small interfering RNA (siRNA) biogenesis

Stable Identifier

R-HSA-426486

Type

Pathway

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Small interfering RNA (siRNA) biogenesis

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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
24388755	RNAi factors are present and active in human cell nuclei Gagnon, KT, Li, L, Chu, Y, Janowski, BA, Corey, DR	Cell Rep	2014
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
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