Production and actions ofsmall RNAs
V. Narry Kim and Mikiko C. Siomi
Small (20–30 nt) RNAs are associated with membersof the Argonaute (Ago) family, which comprises twosubfamilies: Ago and Piwi. Based on their biogenesis
mechanism and the type of Argonaute proteinsthat they associate with, at least three classes ofsmall RNAs can be distinguished in eukaryotes:
microRNAs (miRNAs), endogenous small interfering

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the functions of most piRNAs are still unknown.

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in brackets. miRNAs are ssRNAs of ~22 nt that are generated fromtranscripts that can fold into hairpin structures. Two RNase III type proteins,
Drosha and Dicer, mediate nuclear and cytoplasmic processing, respectively,
thereby producing the miRNAs that subsequently associate with Agosubfamily proteins (AGO1–4 in humans). In flies, most miRNAs are loaded
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into AGO2. exo-siRNAs are derived from experimentally introduced dsRNAs
or viral RNAs. Human exo-siRNAs are loaded onto AGO1–4, but only AGO2
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associate with Piwi-subfamily proteins; they are not dependent on either
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processing differs between mice and flies (for this reason, fly components arenot shown). Primary processing and loading might occur in the cytoplasm
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Table | Eukaryotic small RNAs are associated with Argonaute-family proteins
Subfamily
Mammals
Ago

Ago-family protein

Class of small RNA*

Length of small RNAOrigin of small RNA‡

Mechanism of action

AGO1–4miRNA

21–23 nt

miRNA genes

endo-siRNA§
Pre-pachytene piRNA andpachytene piRNA
Pachytene piRNA
Pre-pachytene piRNA?

21–22 nt
24–28 nt

Intergenic repetitive genes, pseudogenes and endo-siRNA clusters
Transposons and piRNA clusters

Translational repression, mRNA degradation, mRNA cleavage
and heterochromatin formation?
mRNA cleavage?
Heterochromatin formation (DNA methylation)

29–31 nt
27–29 nt?

piRNA clusters
Transposons and piRNA clusters?

?
Heterochromatin formation (DNA methylation)?

AUBAGO3
PIWImiRNA
endo-siRNA
exo-siRNApiRNApiRNApiRNA

21–23 nt
~21 nt~21 nt23–27 nt
24–27 nt
24–29 nt

miRNA genes
Transposons, mRNAs and repeats
Viral genome
Transposons, repeats, piRNA clusters and Su(Ste) locus
Transposons and repeats (unknown in testis)Transposons, repeats and piRNA clusters

Translational repression and mRNA degradation
RNA cleavage
Viral RNA cleavage
RNA cleavage
RNA cleavage
Heterochromatin formation?

Schizosaccharomyces pombe
AgoAgo1

endo-siRNA~21 ntOuter centromeric repeats, mating-type locus andsubtelomeric regions

Heterochromatin formation

miRNA
endo-siRNA (tasiRNA including TAS3)
exo-siRNArasiRNA
miR-390

20–24 nt
21 nt
20–22 nt
24 nt
21 nt

miRNA genes
TAS genes
Viral genome
Transposons and repetitive elements
miRNA genemRNA cleavage and translational repression
mRNA cleavage
Viral RNA cleavage
Heterochromatin formation
Cleavage of TAS3 RNA

Piwi

MILI (PIWIL2 in humans)
MIWI (PIWIL1 in humans)
MIWI2 (PIWIL4 in humans)(PIWIL3 in humans)

Drosophila melanogaster
Ago

Piwi

Arabidopsis thaliana||Ago

AGO1
AGO2

AGO1

AGO4 and AGO6
AGO7

*Small RNAs that are the main partners of a given Ago protein are listed. ‡miRNAs, as a class, are expressed in all cell types, whereas endo-siRNAs and piRNAs are expressed abundantly in germline cells and contribute to germline development.
§So far, only AGO2 has been shown to be required for endo-siRNAs. ||Plants have ten Ago proteins, but only those with known small RNA partners are shown.

Components of the RISC complex at Abcam
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nrm_poster_feb09.indd 1

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Abbreviations

Contact information

Ago, Argonaute; AUB, Aubergine; CCR4, C-C chemokine type 4; DGCR8,DiGeorge syndrome critical region gene 8; DNMT, DNA methyltransferase;dsRNA, double-stranded RNA; endo-siRNA; endogenous small interfering
RNA; exo-siRNA, exogenous small interfering RNA; H, histone;
HMT, histone methyltransferase; HP1, heterochromatin protein 1;
LOQS, Loquacious; m7G, 7-methylguanosine; Me, methyl; miRNA,microRNA; nt, nucleotide; piRNA, Piwi-interacting RNA; Pol II, RNApolymerase II; PACT, PKR-activating protein; pre-miRNA, precursor miRNA;
pri-miRNA, primary miRNA; rasiRNA, repeat-associated small interfering
RNA; ssRNA, single-stranded RNA; Su(Ste), Suppressor of Stellate; TAS, tasi
gene; tasiRNA, trans-acting siRNA; TRBP, HIV-1 TAR RNA-binding protein.

V. Narry Kim is at the School of Biological Sciences and Center for
National Creative Research, Seoul National University, Seoul, 151-742,South Korea. | Mikiko C. Siomi is at Keio University School of Medicine,
35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, and at the Japan Scienceand Technology Agency (JST), Core Research for Evolutional Science andTechnology (CREST), Saitama 332-0012, Japan.
e-mails: narrykim@snu.ac.kr; siomim@sc.itc.keio.ac.jp

Poster design by Vicky Askew, edited by Arianne Heinrichs,
copyedited by Simon Bishop. © 2009 Nature Publishing Group.

Kim, V. N., Han, J. & Siomi, M. C. Biogenesis of small RNAs in animals.
Nature Rev. Mol. Cell Biol. (doi:10.1038/nrm2608).

For further reading, see www.nature.com/nrm/posters/smallrnas

Linked review article

1/12/08 11:42:02