Biology Reference
In-Depth Information
Chapter 5
Computational Biology of Small
Regulatory RNAs
Mihaela Zavolan and Lukasz Jaskiewicz
1. Introduction
The discovery of the let-7 microRNA (miRNA) and the realization that
small RNA regulators are conserved over large evolutionary distances
1,2
prompted a vast number of studies aiming to uncover these molecules
across species and to characterize their function. Specialized protocols for
isolation of miRNAs
3-5
lead to the identification of large numbers of
mammalian miRNAs whose function — in contrast to that of the founder
of the class, the lin-4 miRNA
6
— has yet to be discovered. Nonetheless,
initial efforts aimed to generate catalogs of miRNAs in various species.
miRNAs associate with Argonaute members of the PAZ/PIWI domain
(PPD) family of proteins to form RNA-induced silencing complex
(RISC)-like ribonucleotide particles,
7,8
which have also been observed
during silencing that occurs upon injection of small interfering RNAs
(siRNAs). The first members of the PPD family to be characterized were
Argonaute-1 and Zwille in
Arabidopsis thaliana
.
9,10
The genome of
the worm
Caenorhabditis elegans
encodes a total of 27 PPD proteins; the
mouse genome, 7; and the human genome, 8.
It appears that PPD proteins evolved to perform highly specialized
functions that vary widely between species. In humans, for instance four
PPD proteins (Ago-1 through Ago-4) bind miRNAs, but only Ago-2 has
the catalytic activity required for the mRNA cleavage,
7,8
typically
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