- HIV-1 in the RNA world: Transcription regulation, miRNAs and antiviral RNAs
- Award date
- 30 April 2015
- Number of pages
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
All organisms, from bacteria to human, use three biological molecules that each serve critical functions in the expression of genes in the cell. These are deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and proteins. RNA is synthesized from DNA in a process called transcription. RNA differs from DNA in that it is composed of ribose instead of deoxyribose sugars, it contains Uracil instead of Thymine and it is mostly single-stranded (ss) instead of double-stranded (ds). The flow of genetic information in a cell is from DNA through RNA to proteins, thus DNA makes RNA makes protein. The genetic information in the form of DNA in the nucleus is connected by the messenger RNA (mRNA) to the protein-producing ribosomes in the cytoplasm. But RNA molecules play many more critical functions in the cell, e.g. it forms the enzymatic and structural component of ribosomes (rRNA) and the translational building blocks (tRNA), and is the main effector of post-transcriptional gene regulation (via microRNAs or miRNAs in the RNA interference (RNAi) mechanism). RNA also serves as the genetic material for many clinically relevant viruses like Ebola virus, hepatitis C virus and the human immunodeficiency virus type I (HIV-1).
In this thesis, some known and novel RNA functions are investigated with HIV-1 as model system. The main focus of this work is on the mechanism of HIV-1 transcription, the RNAi pathway and the interplay between both. Therefore, to understand this thesis, the general biology of HIV-1 will first be covered, after which the mechanism of transcription and RNAi will be explained in more detail.
- Research conducted at: Universiteit van Amsterdam
Chapter 6: Tat-dependent production of an HIV-1 TAR-encoded miRNA by a non-canonical miRNA pathway (Embargo until 30 April 2017)
Chapter 8: Deep sequence analysis of AgoshRNAs reveals 3’ A-addition and trimming (Embargo until 30 April 2017)
Chapter 9: Towards optimization of AgoshRNA molecules that use a non-canonical RNAi pathway: variations in the top and bottom base pairs (Embargo until 30 April 2017)
Chapter 10: Mechanistic insights on the Dicer-independent AGO2-mediated processing of AgoshRNAs (Embargo until 30 April 2017)
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