Download High-Resolution Profiling of Protein-RNA Interactions by Mathias Munschauer PDF

By Mathias Munschauer

The paintings suggested during this booklet represents a good instance of ways artistic experimentation and expertise improvement, complemented by way of computational facts research, can yield very important insights that extra our knowing of organic entities from a structures point of view. The e-book describes how the research of a unmarried RNA-binding protein and its interplay websites resulted in the advance of the radical ‘protein occupancy profiling’ know-how that for the 1st time captured the mRNA series area contacted by way of the ensemble of expressed RNA binders. program of protein occupancy profiling to eukaryotic cells printed that broad series stretches in three’ UTRs could be contacted by way of RBPs and that evolutionary conservation in addition to destructive choice act on protein-RNA touch websites, suggesting sensible value. Comparative research of the RBP-bound series area has the aptitude to resolve putative cis-acting RNA components and not using a priori wisdom of the certain regulators. right here, Dr. Munschauer presents a accomplished advent to the sector of post-transcriptional gene law, examines cutting-edge applied sciences, and combines the conclusions from a number of magazine articles right into a coherent and logical tale from the frontiers of systems-biology encouraged lifestyles technology. This thesis, submitted to the dept of Biology, Chemistry and Pharmacy at Freie Universität Berlin, used to be chosen as extraordinary paintings by means of the Berlin Institute for clinical structures Biology on the Max-Delbrueck middle for Molecular medication, Germany.

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2008; Stark et al. 2005). Interestingly, the expression level of mature miRNAs is not typically coupled to the expression of its precursor transcripts, indicating that miRNA biogenesis itself is under post-transcriptional control. Among the historically first examples of such regulation is the RNA-binding protein Lin28 that inhibits miRNA let-7 biogenesis (Heo et al. 2008; Newman et al. 2008) (for details see Sect. 4). Today, the Lin28-let-7 axis represents one of the best-studied examples of a post-transcriptional gene-regulatory mechanism that is highly conserved throughout evolution and has pivotal roles in development and differentiation (Thornton and Gregory 2012; Viswanathan and Daley 2010).

2011). To further investigate the requirement of Lin28A for normal glucose metabolism in one specific adult tissue, transgenic mice with muscle-specific loss of Lin28A protein or inducible expression of ectopic let-7 were generated (Zhu et al. 2011). In contrast to Lin28A overexpressing animals, muscle-specific knockout mice displayed glucose intolerance and insulin resistance. Furthermore, the same study showed that regulation of glucose metabolism occurs via let-7-mediated repression of the insulinPI3 K-mTOR pathway (Zhu et al.

2014). Additional evidence that m6A might influence transcript stability was provided by knockdown experiments that targeted the methyltransferases METTL3 and METTL14 (Liu et al. 2014). In conclusion, the existence of ‘writer’, ‘reader’ and ‘eraser’ proteins suggests complex and dynamic regulation of m6A levels throughout the life cycle of an RNA molecule. Less is known about the regulation of 5-methylcytosine. Two m5C-specific methyltransferases (NSUN2 and TRDMT1) that predominantly target tRNA, but 24 1 Introduction might also act on mRNA have been described so far (Sibbritt et al.

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