Regulation of microRNAs - H. Grosshans (Landes, 2010) WW.pdf

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Regulation of microRNAs

ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY

Editorial Board:

NATHAN BACK,

State University of New York at Buffalo

IRUN R. COHEN,

The Weizmann Institute of Science

ABEL LAJTHA,

N.S. Kline Institute for Psychiatric Research

JOHN D. LAMBRIS,

University of Pennsylvania

RODOLFO PAOLETTI,

University of Milan

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Volume 700

REGULATION OF MICRORNAS

Helge Großhans

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Regulation of microRNAs

Edited by

Helge Großhans

Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland

Springer Science+Business Media, LLC

Landes Bioscience

Springer Science+Business Media, LLC

Landes Bioscience

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Regulation of microRNAs,

edited by Helge Großhans. Landes Bioscience / Springer Science+Business Media,

LLC dual imprint / Springer series: Advances in Experimental Medicine and Biology.

ISBN: 978-1-4419-7822-6

of equipment and devices, as set forth in this book, are in accord with current recommendations and practice

at the time of publication, they make no warranty, expressed or implied, with respect to material described

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Library of Congress Cataloging-in-Publication Data

Regulation of microRNAs / edited by Helge Grosshans.

p. ; cm. -- (Advances in experimental medicine and biology ; v. 700)

Includes bibliographical references and index.

ISBN 978-1-4419-7822-6

1. Small interfering RNA. 2. Genetic regulation. I. Grosshans, Helge. II. Series: Advances in experimental

medicine and biology ; v. 700. 0065-2598

[DNLM: 1. MicroRNAs--genetics. 2. Gene Expression Regulation--genetics. W1 AD559 v.700 2010 / WY 105]

QP623.5.S63R445 2010

572.8’8--dc22

2010038832

PREFACE

When in 2001 the first draft versions of the human genome revealed that there were no

more than 25,000 human genes, much soul searching resulted. How could a complicated

human being develop and function with a gene set not much bigger than that of a worm,

Caenorhabditis elegans?

Although the meaning of ‘gene counts’ is debatable when a single gene can give rise to

a multitude of different gene products (and when in fact much of the ‘inter-genic’ genome

appears to be transcribed), the apparent conundrum highlighted the importance of gene

regulation in making complex organisms. It thus appears particularly appropriate that it

was also in 2001 that microRNAs (miRNAs) were finding their way into the limelight.

These regulatory RNAs, named for their small size of some 22 nucleotides, had been

discovered in 1993 in

C. elegans,

but were initially considered a worm oddity and largely

ignored. It was only when small RNA cloning efforts started to reveal hundreds of different

miRNAs in a typical animal or plant genome that they were widely noticed. Today, it

appears that hardly any cellular or developmental pathway has escaped the control that

miRNAs exert by silencing target mRNAs through an antisense mechanism. Accordingly,

miRNAs dysregulation contributes to numerous diseases, most notably diverse cancers.

Given this pervasiveness and importance of miRNA-mediated gene regulation,

it should come as little surprise that miRNAs themselves are also highly regulated.

However, the recent explosion of knowledge on this topic has been remarkable, providing

a primary motivation for publication of this book. As miRNAs are transcribed by RNA

polymerase II, the enzyme that also generates mRNAs, it was perhaps not unexpected

that miRNA transcription would be subject to regulation, and we have willfully omitted

this aspect from this monograph. However, what has been unexpected is the extent of

post-transcriptional regulation of miRNAs that is illustrated in this book.

In the first chapter, René Ketting provides the background against which all of the

regulatory processes occur by revealing the complex biogenesis and function of miRNAs

and the related siRNAs. Akiko Hata and Brandi Davis then describe how SMAD proteins,

generally known for their function in controlling transcription, reveal another side in

regulating the processing of certain primary miRNA (pri-miRNA) transcripts by the

Regulation of microRNAs - H. Grosshans (Landes, 2010) WW.pdf

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