Discovery and profiling of animal small RNAs using deep sequencing

Discoveries in the last decade have shown that small RNAs (such as microRNAs) perform a number of important functions, including post-transcriptional gene regulation, transposon silencing, DNA methylation, chromatin modifications and chromosome segregation. The ability of the new deep sequencing technologies to sequence millions of short RNAs in a few hours have made them the method of choice for simultaneous discovery and profiling of small RNAs. However, when the sequenced RNAs are mapped to the reference genome, they typically locate to millions of distinct loci, only a few of which are loci that produce regulatory small RNAs. To distinguish the few loci that produce regulatory small RNAs from the many loci that are sources of other short RNAs like degradation products is a non-trivial computational challenge. In my doctorate works I have formalized knowledge of small RNA biology and biogenesis into computational models that can accurately identify regulatory small RNAs of different classes in much larger pools of sequenced RNAs. As part of collaborations, I have used these models to discover hundreds of novel small RNA genes in more than ten animal species including humans, mice, fruit flies, nematodes and planarian flatworms. We find evidence that a number of these small RNA genes have roles in disease or in stem cell function. Further, some of the novel regulatory small RNAs are in fact cleaved bona fide snoRNAs, revealing cross-talk between two RNA pathways. Last, I have developed methods for precise quantitation of individual small RNAs as well as entire small RNA populations between deep sequencing samples.

Author dc:creator

• Friedländer, Marc Riemer

• miRNAs
• piRNAs
• small RNAs
• deep sequencing
• bayesian statistics

Licence dc:rights.uri

• http://www.fu-berlin.de/sites/refubium/rechtliches/Nutzungsbedingungen

Language dc:language

eng

Identifier URI

http://dx.doi.org/10.17169/refubium-5559

OAI record oai:identifier

https://refubium.fu-berlin.de/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Arefubium.fu-berlin.de%3Afub188%2F1357