Dicor

(Dicor 1 in fios)
1k8l or lAC1
(LOQS in fios)
mikNA gene pikNA |oci (intergenic repetitive genes, active transposon genes and pikNA c|usters)
+
- -
+ +
-
+
- -
endo-sikNA |oci (intergenic repetitive genes, pseudogenes and endo-sikNA c|usters)
mikNA endo-sikNA eo-sikNA
Fxporf
Dicinq
pre-mikNA
(AGO1 in fios)
AAAAA

Droshu
DGCk8 (lushu in fios)
1runscripfion 1runscripfion 1runscripfion
Croppinq
m
1
G
Fxporfin S-
kunG1l
Dicor (Dicor 2 in fios)
Fxoqonous dskNA
1k8l or lAC1?
(LOQS in fios)
Dicor (Dicor 2 in fios)
AGO1-4
pikNA procursors ondo-sikNA procursors
1runscripfion
Loudinq
Socondury
procossinq

lrimury
procossinq
MlWl2 MlWl2
MlWl2
MlWl2
MlLl MlLl
MlLl
lrimury
procossinq
Loudinq
MlWl
MlLl
MlWl
MlLl
-dskNA -dskNA Huirpin-fypo
(AGO2 in fios) (AGO2 in fios) AGO1-4 AGO1-4 AGO2 AGO2
?
?
?
?
1k8l or lAC1?
(k2D2 in fios)
Nuclous
Cyfoplusm
Possible mechanisms of action
Aqo Aqo
AAAAA AAAAA
mkNA c|eavage
(mikNA und ondo-sikNA?)
1rans|ationa| repression
(mikNA)
Aqo
AAAA
Deadeny|ation and mkNA degradation
(mikNA)
Heterochromatin formation (DNA methy|ation and/or histone modi6cation)
(pikNA und mikNA?)
CCk4-NO1
liwi/Aqo
Mo
DNM1
Mo Mo
HM1
H H H
Mo Mo
Hl1
H
l
1
lol ll
liwi/Aqo
lol ll
m
1
G
kibosomo
*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.
Production and actions of
small RNAs
V. Narry Kim and Mikiko C. Siomi
Small (2030 nt) RNAs are associated with members
of the Argonaute (Ago) family, which comprises two
subfamilies: Ago and Piwi. Based on their biogenesis
mechanism and the type of Argonaute proteins
that they associate with, at least three classes of
small RNAs can be distinguished in eukaryotes:
microRNAs (miRNAs), endogenous small interfering
RNAs (endo-siRNAs) and Piwi-interacting RNAs
(piRNAs). miRNAs control mRNA stability and
translation by targeting cognate mRNAs. endo-
siRNAs suppress repetitive genes by cleaving their
transcripts. Some piRNAs mediate RNA cleavage or
heterochromatin formation of transposons, although
the functions of most piRNAs are still unknown.
Abcam is able to deliver a comprehensive portfolio of all the
very best and most up to date antibodies to components of
the RISC complex. We are constantly increasing the number
of ChIP-grade and batch tested antibodies, enabling the
research community to deconstruct epigenetic pathways.
Three of our very best Dicer and Ago antibodies:
Dicer 1 (ab13502)
Ago1 (Drosophila) (ab5070)
Ago2 (Drosophila) (ab5072)
Two of our very best RISC antibodies:
TRBP (ab42018)
DDX6 (ab40684)
All our antibodies to the components of the RISC complex are
highly characterized and our datasheets provide a library of
relevant information.
Investigate these and other chromatin and RNAi antibodies
further at www.abcam.com/RISC
The Abpromise
If our antibodies do not perform as described on the
datasheet, notify us within 4 months of delivery so we can
help you or offer a replacement or a refund.
Abbreviations
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; m
7
G, 7-methylguanosine; Me, methyl; miRNA,
microRNA; nt, nucleotide; piRNA, Piwi-interacting RNA; Pol II, RNA
polymerase 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.
Poster design by Vicky Askew, edited by Arianne Heinrichs,
copyedited by Simon Bishop. 2009 Nature Publishing Group.
Contact information
V. Narry Kimis 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 Science
and Technology Agency (JST), Core Research for Evolutional Science and
Technology (CREST), Saitama 332-0012, Japan.
e-mails: narrykim@snu.ac.kr; siomim@sc.itc.keio.ac.jp
For further reading, see www.nature.com/nrm/posters/smallrnas
Linked review article
Kim, V. N., Han, J. & Siomi, M. C. Biogenesis of small RNAs in animals.
Nature Rev. Mol. Cell Biol. (doi:10.1038/nrm2608).
Components of the RISC complex at Abcam
Table | Eukaryotic small RNAs are associated with Argonaute-family proteins
Subfamily Ago-family protein Class of small RNA* Length of small RNA Origin of small RNA

Mechanism of action
Mammals
Ago AGO14 miRNA 2123 nt miRNA genes Translational repression, mRNA degradation, mRNA cleavage
and heterochromatin formation?
endo-siRNA

2122 nt Intergenic repetitive genes, pseudogenes and endo-siRNA clusters mRNA cleavage?
Piwi MILI (PIWIL2 in humans) Pre-pachytene piRNA and
pachytene piRNA
2428 nt Transposons and piRNA clusters Heterochromatin formation (DNA methylation)
MIWI (PIWIL1 in humans) Pachytene piRNA 2931 nt piRNA clusters ?
MIWI2 (PIWIL4 in humans) Pre-pachytene piRNA 2729 nt Transposons and piRNA clusters Heterochromatin formation (DNA methylation)
(PIWIL3 in humans) ? ? ? ?
Drosophila melanogaster
Ago AGO1 miRNA 2123 nt miRNA genes Translational repression and mRNA degradation
AGO2 endo-siRNA ~21 nt Transposons, mRNAs and repeats RNA cleavage
exo-siRNA ~21 nt Viral genome Viral RNA cleavage
Piwi AUB piRNA 2327 nt Transposons, repeats, piRNA clusters and Su(Ste) locus RNA cleavage
AGO3 piRNA 2427 nt Transposons and repeats (unknown in testis) RNA cleavage
PIWI piRNA 2429 nt Transposons, repeats and piRNA clusters Heterochromatin formation?
Schizosaccharomyces pombe
Ago Ago1 endo-siRNA ~21 nt Outer centromeric repeats, mating-type locus and
subtelomeric regions
Heterochromatin formation
Arabidopsis thaliana
||
Ago AGO1 miRNA 2024 nt miRNA genes mRNA cleavage and translational repression
endo-siRNA (tasiRNA including TAS3) 21 nt TAS genes mRNA cleavage
exo-siRNA 2022 nt Viral genome Viral RNA cleavage
AGO4 and AGO6 rasiRNA 24 nt Transposons and repetitive elements Heterochromatin formation
AGO7 miR-390 21 nt miRNA gene Cleavage of TAS3 RNA
The figure shows the mammalian processing pathways with fly components
in brackets. miRNAs are ssRNAs of ~22 nt that are generated from
transcripts 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 Ago-
subfamily proteins (AGO14 in humans). In flies, most miRNAs are loaded
onto AGO1, whereas miRNAs from highly base-paired precursors are sorted
into AGO2. exo-siRNAs are derived from experimentally introduced dsRNAs
or viral RNAs. Human exo-siRNAs are loaded onto AGO14, but only AGO2
has slicer activity. endo-siRNAs are derived from cis or trans sense
antisense dsRNAs or long hairpins. They are produced by Dicer and interact
with Ago-subfamily proteins. In humans, endo-siRNAs are thought to be
loaded onto AGO2; it has not been determined whether they associate with
other Ago proteins. piRNAs (2431 nt) are processed from ssRNA precursors
that are transcribed from transposons or large piRNA clusters. piRNAs
associate with Piwi-subfamily proteins; they are not dependent on either
Drosha or Dicer, although the requirement of Drosha has not been formally
tested. They may instead use the nuclease activity of the Piwi proteins
themselves for their processing. piRNA biogenesis involves primary and
secondary processing mechanisms. The strand bias of piRNAs in secondary
processing differs between mice and flies (for this reason, fly components are
not shown). Primary processing and loading might occur in the cytoplasm
because Piwi proteins MIWI and MILI are localized in the cytoplasm. Factors
that are needed for primary processing are unknown. Not shown here are less
abundant groups of miRNA-like RNAs that are derived from various sources
of short hairpins in a Drosha-independent manner.
MOLECULAR
CELL BIOLOGY
2009 Macmillan Publishers Limited. All rights reserved