RNA and gene regulation (2310)

title prof.dr. Sc. Lily of the Valley, zn. Advisor-permanent choice

Rudjer Boskovic Institute, Department of Molecular Biology

Understand ncRNA as key molecules in programmed regulation of gene activity and learn the functions of different classes of ncRNA molecules in the eukaryotic genome.

1. Basics of transcription in eukaryotes: RNA polymerases I, II, III and IV. 2. The maturation of transcripts in eukaryotes, the role of snRNA (the "small nuclear RNA") and the mechanism of alternative substitution ("alternative splicing"). 3. Overview of the most important classes of ncRNA and their roles: a) ribosomal (rRNA) and transfer (tRNA) RNA in protein biosynthesis. b) small nucleolar RNA or snoRNA («small nucleolar RNA»): mechanism of modification of rRNA, tRNA and snRNA. c) micro RNA (miRNA): mechanism of formation from double-stranded precursors and inhibitions of target mRNA-RNA interference (RNAi) translations. d) small interfering RNA (siRNA of "small interfering" RNA), origin, emergence and mechanism of action in the protein complex: structure of RISC («RNA induced silencing «) complex and RITS («RNA induced transcription silencing») complex. Reproduction of siRNA by the action of RDRC («RNA directed RNA polymerase») complex 4. siRNA as a signal for epigenetic modifications of DNA and DNA binding proteins – mechanism of formation and types of epigenetic modifications. Epigenetic regulation of gene activity: "sedation" of genes and parts of the genome. 5. Disorders in epigenetic modifications and the onset of the disease. The importance of epigenetic modifications in the onset of cancer and a new therapeutic strategy based on the reversal of epigenetic modifications. 6. Inactivation of X chromosomes: the role of Xist RNA ("X-inactive specific transcript") and Tsix RNA (antisens on Xist). The role of antisens RNA in the regulation of gene activity. Functional transcripts of pseudogenes and their role in translation. Ribookids ("Riboswitches") that influence gene activity by binding specific ligands. 7. Epigenetic phenomenon of genomic "imprinting" leading to differential expression of alleles and its possible association with small RNA (siRNA, miRNA and snoRNA).

1. To analyze the role of different classes of non-coding molecules of RNA n(cRNA) in programmed and very complex regulation of gene activity in eukaryotes, in the evolution of complex eukaryotic systems, embryogenesis, the development and functioning of the living system and in the emergence of various diseases.
2. Explain the mechanism of action of different types of non-coding RNA at the molecular level.
3. Select relevant literature sources and interpret scientific data critically.

Regular attendance and mandatory seminar work.

To follow the course, basic knowledge about the transfer of genetic information that can be obtained in the course "Biochemistry" or "Basics of Molecular Biology" is required.

Book:
Ugarković, D. (editor) Long Non-Coding RNAs. Prog Mol Subcell Biol. Ox. 51; 2011; Springer Verlag Heidelberg. ISBN 978-3-642-16501-6

Scientific papers:
1. Lee J & Bartolomei S (2013) X-Inactivation, Imprinting, and Long Noncoding RNAs in Health and Disease. Cell 152: 1308-23
2. Batista PJ & Chang HY (2013) Long Noncoding RNAs: Cellular Address Codes in
Development and Disease. Cell 152: 1298-1307.
3. Mercer T & Mattick J (2013) Structure and function of long noncoding RNAs in epigenetic
Regulation. Nature Struct. & Mol. Biol 20: 300-7.
4. Fatica A, Bozzoni I (2014) Long non-coding RNAs: new players in cell differentiation and
development. Nature Rev. Gene. 15: 7-21.
5. Mendell J.T., Olson EN. (2012) MicroRNAs in Stress Signaling and Human Disease.
Cell 148: 1172-87.
6. Jonas S, Izzauralde E (2015) Towards a molecular understanding of microRNA- Mediated gene silencing. Naure Rev. Gene. 16: 421- 433.
7. Ventura et al. (2009) MicroRNAs and Cancer: Short RNAs Go a Long Way. Cell 136: 586-91
8. Carthew et al. (2009) Origins and Mechanisms of miRNAs and siRNAs . Cell 136: 642-55
9. Holoch D, Moazed D. (2015) RNA-mediated epigenetic regulation of gene expression. Nature Rev. Gen.16: 71-84.
10. Pezer Ž. & Ugarković Đ. (2008) Role of non-coding RNA and heterochromatin in Aneuploidy and cancer. Seminars Cancer Biol 18: 123-130
11. Siomi I et al. (2011) PIWI-interacting small RNAs: the vanguard of genome defence. Nature Rev. Breakwater. Cell Biol. 12: 247-258

1. Luteijn MJ, Ketting RF. (2013) PIWI-interacting RNAs: from generation to transgenerational epigenetics. Nature Rev. Gene. 14: 523-534.
2. Siena G et. Al. (2012) Transcriptional Silencing of Transposonsby Piwi and Maelstrom and Its Impact on Chromatin State and Gene Expression. Cell 151: 964-80
3. Feliciello I, Akrap I, Ugarković Đ. (2015) Satellite DNA Modulates Gene Expression in the Beetle Tribolium castaneum after Heat Stress. PLoS Genet. 11(8): e1005466.
4. Gall Trošelj K, Novak Kujundžić R, Ugarković Đ. (2016) Polycomb Repressive Complex's Evolutionary Conserved Function: the Role of EZH2 Status and Cellular Background. It's Clin. Epigenetics 8: 55.

Discussions with students on the basis of which the understanding of the information obtained is verified. The obligatory presentation of the seminar paper based on the analysis of original scientific papers testifies to the degree of adoption and understanding of the material.
The success of the course will be evaluated annually by the joint expert committee of the Rudjer Boskovic Institute, the University of Dubrovnik and the University of Osijek.