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Posttranscriptional Regulation of the Microrna-17-92a Cluster
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Dissertation
Posttranscriptional Regulation of the Microrna-17-92a Cluster
2013
Overview
By far not all genetic information is expressed by mRNA coding regions of the DNA. 98% of the human genome is not encoding for proteins. Therefore, these non-coding regions have been considered as “junk DNA” for a long time [1, 2]. The last years, new high throughput sequencing techniques have allowed the elucidation of the heterogeneous population of non-coding RNAs (ncRNAs, Table 1). RNAs longer than 200 nucleotides (nt) belong to the family of long non-coding RNAs (lncRNAs). They can exhibit numerous functions: The biggest family of RNAs is represented by the ribosomal RNAs (rRNAs). Together with the transfer RNAs (tRNAs) they are essential for the translation of mRNA into an amino acid sequence.The most popular example of a functional lncRNA is Xist, a lncRNA that mediates the inactivation of the second X-chromosome in females [3]. By now, numerous functions have been assigned to lncRNAs, e.g. epigenetic regulation of gene expression or splicing [4, 5] and are deregulated in disease states, e.g. MALAT1 has been shown to be involved in the pathogenesis of pulmonary tumors [6]. However, the function of many lncRNAs remains unknown. Small non-coding RNAs are shorter than 200 nucleotides. For example, small nuclear RNAs (snRNAs or U-RNAs) are located in the nucleus where they regulate the processing of mRNAs. Small nucleolar RNAs (snoRNAs) and small cajal body specific RNAs (scaRNAs), as well are able to guide modifications of other RNAs, especially methylation and pseudouridylation of rRNAs, tRNAs and snRNAs. Piwi-interacting RNAs (piRNAs) are the largest group of small non-coding RNAs. They are present in complexes with proteins and function as epigenetic gene regulators in germ cells [7]. Moreover they are implicated in transposon silencing and heterochromatin modification [8]. MicroRNAs are another large group of small non-coding RNAs, that was investigated extensively within the last two decades. The biogenesis and regulation as well as the function of miRs will be introduced in the following sections.
Publisher
ProQuest Dissertations & Theses
Subject
