Genome-wide characterization of the complex trancriptome architecture of S. cerevisiae with tiling arrays [Elektronische Ressource] / presented by Marina Granovskaia

Maria Granovskaia

Sujets

• Biologie

Informations

• Publié par: ruprecht-karls-universitat_heidelberg
• Publié le: 01 janvier 2008
• Nombre de lectures: 26
• Langue: English
• Poids de l'ouvrage: 4 Mo

Extrait

Genome-wide Characterization of the Complex Transcriptome
Architecture of S. cerevisiae with Tiling Arrays











Marina Granovskaia

2008



Dissertation


Submitted to the
Combined Faculties for the Natural Sciences and for Mathematics
of the Ruperto-Carola University of Heidelberg, Germany
for the degree of
Doctor of Natural Sciences








presented by
Diploma-Biochemist Marina Granovskaia
Born in Moscow, Russia



Oral examination: 15 February 2008









Genome-wide Characterization of the Complex Transcriptome
Architecture of S. cerevisiae with Tiling Arrays












Referees: Dr. Blanche Schwappach, ZMBH, University of Heidelberg
Dr. Peer Bork, EMBL, Heidelberg Acknowledgements

Acknowledgements

I would like to thank Dr. Lars Steinmetz for giving me the opportunity to work in his lab towards my
PhD thesis. I am grateful for Lar’s continuous support throughout my thesis work, his original ideas, and
our intensive and constructive discussions, for his encouragements and understanding in the critical
moments, for his contagious enthusiasm about new discoveries and passion about science. I value that
Lars would never let me alone in the moments of hesitations, but would always promote my
independence to develop my own ideas and fulfill them. I want to thank Lars for a wonderful opportunity
to work at the Stanford University Genome Technology Center as part of the scientific collaboration in
our lab. That has been an unforgettable scientific and personal experience for me and I want to thank all
the SGTC team who made it as such. Working with you, Lars has always been a complete intellectual
involvement and enjoyment!
I would like to thank Dr. Blanche Schwappach and Dr. Peer Bork for their continuous support, fruitful
discussions and constructive advice in my thesis advisory committees and for agreeing to evaluate my
thesis.
I would like to thank Dr. Wolfgang Huber for his advice on the bioinformatics part of the projects and
for giving me the opportunity to work with excellent members of his team in a productive collaboration.
I would also like to thank Dr. Jochen Wittbrodt for agreeing to be on my defense committee and for
giving me very helpful advice on the preparation for the defense.
I want to thank Dr. Paul Bertone for agreeing to be on my thesis defense committee.
I want to thank Dr. Martina Muckenthaler for being on my thesis advisory committees and for the
constructive discussions therein as well as for her personal and professional advice.
I am particularly grateful to Dr. Matt Ritchie for constantly providing me with bioinformatics support,
for thoroughly finding and trying new approaches to analyze my data. I thank Matt for great help in
generating several figures for my thesis and for always supporting me in testing new things in the
analysis of the data. It has been a pleasure working together with you!
I would like to thank Dr. Lars Juhl Jensen for an extremely fruitful collaboration on the cell cycle
project, for producing an excellent and fast analysis of my datasets and sharing his broad expertise on the
regulation of the cell cycle.
Very special words of appreciation go to Dr. Vladimir Benes for his great help and critical ideas
throughout constant optimizations of hybridization procedure that I was doing in my PhD; for his
readiness to support me in facing any intellectual challenges that I encountered and sharing his expertise
I Table of Contents

of the subject, for pushing me to think out of the established frames of the techniques in order to find
new solutions. I also thank Vladimir for his endless support and encouragements.
Many thanks to Tomy Ivacevic for his help with technical details and other tips and tricks; thanks for his
advice on hybridizations and for always being ready to devote his time. Thanks to all other members of
the GeneCore facility for creating a pleasant atmosphere to work with and for their readiness to help.
I would like to thank all of the members of the Steinmetz Lab for making my years here an enjoyable
time. They are: Sandra Clauder-Muenster, Ye Ning, Rui Wang, Zhenyu Xu, Himanshu Sinha, Eugenio
Mancera, Fabiana Perocchi, Julien Gagneur, Stephanie Blandin, Raeka Aiyar, Wu Wei, Stefan
Mockenhaupt, and Stefan Wilkening. Special thanks go to Sandra Clauder-Muenster and Ye Ning for
their technical support and fruitful discussions on the new techniques and to Rui Wang for her support,
encouragement and sharing wise life perspectives.
I would like to particularly like to thank Dr.Yury Belyaev and Dr.Arne Seitz from the ALMF facility for
their diligent help with electron microscopy imaging and processing.
I would like to thank Bernadett Papp, Janina Karres, Philipp Gebhardt and Yevheny Vainshtein for their
friendship and support. I want to thank Yevheny for his continuous help with computational stuff. I
would like to thank a lot to Helio Roque for his great help as well.

Огромное спасибо мои м замечательным родителям и бабу шк е за поддержк у во время всех лет
учёбы, за бесконечн ую веру в меня. Спаси бо за Вашу любовь и др у жбу и за критик у, которая
помогала мне осознавать поворотные момент ы моей жизни.
Спасибо Бо ре за терпение и поддержк у в течение этих лет и за то, что ты всегда пытался внести в
мою жизнь внешний баланс, выры вая из кру га бесконечн ы х задач по работе.
Спасибо моему сын у Марк у за то, что он стал ещё одним веским поводом и вдохновением
добиться карьерного усп ех а, за то, что он дал мн е понять, что как бы ни бы ло сложно, в жизни
есть непреходящие ценности, которые делают её счастливой и насыщенной. Спасибо за то, что
ещё ничего не понимая, ты терпел моё отсу тст вие, когда я была ну жна тебе боль ше всего!

Thanks to everyone else who is not mentioned here due to space limitations, but who has made this work
possible and supported me throughout these years!

II Table of contents

Table of Contents
Acknowledgments .......................................................................................................................................I
Table of Contents...... III
Summary...................VII
Zusammenfassung.....IX
1. Itroduction........... 1
I. Challenging Dogmas ...................................................................................................................... 2
II. Non-coding RNAs........................................................................................................................... 4
1. Infrastructural RNAs................................................................................................................. 4
1.1 Transfer RNA (tRNA).......................................................................................................... 4
1.2 Ribosomal RNA (rRNA)...................................................................................................... 5
1.3 Small nucleolar RNAs (snoRNAs) ...................................................................................... 7
1.4 Small nuclear RNA (snRNA)............................................................................................... 9
2. Regulatory Non-coding RNAs................................................................................................. 10
2.1 Bacterial stealth regulators................................................................................................. 13
2.1.1 Cis-ncRNAs ............................................................................................................... 13
2.1.2 Trans-ncRNAs. .......................................................................................................... 15
2.2 RNA intereference by double-stranded RNA .................................................................... 17
2.2.1 Interferone response................................................................................................... 17
2.2.2 RNAi and siRNAs...................................................................................................... 17
2.2.3 RNA editing............................................................................................................... 21
2.3 Micro RNAs (miRNA)....................................................................................................... 21
2.3.1 A short history of miRNAs ........................................................................................ 21
2.3.2 miRNA biogenesis..................................................................................................... 23
2.3.3 Regulation of gene expression by miRNAs............................................................... 25
2.3.4 miRNAs and human diseases..................................................................................... 27
2.4 Other ncRNAs.................................................................................................................... 28
2.4.1 Mechanisms of sense-antisense correlated regulation and their