Jürgen Brosius

In the early 1980s, Brosius became interested in a small brain-specific RNA that was thought to be a waste product of a mechanism orchestrating the expression of genes by RNA polymerase III transcription of identifier sequence (ID) repetitive elements, classified as SINEs, short interspersed repeats, located in the introns of brain-specific genes by making chromatin accessible to RNA polymerase II.[12] This attractive hypothesis was not tenable. Instead, the Brosius laboratory focused on this brain cytoplasmic BC1 RNA, cloned it as cDNA by developing a method for generating cDNA libraries based on non-polyadenylated RNAs, and isolated its single gene, which evolved from a retroposed copy of a transfer RNA (tRNA^Ala). It was shown that BC1 RNA is the source gene for ID repetitive elements in rodents, and his laboratory established that the dendritic localization of BC1 RNA in neurons[13][14][15] co-localizes with numerous components of the translation machinery.[16] Based on these findings, Brosius concluded as early as the eighties that:

1. Functional RNAs are not only fossils from a by-gone RNA world[17] but can arise de novo in modern cells and contribute to the functionality of a cell or organism; many more RNAs are yet to be discovered.

2. Retroposition (conversion of RNA to DNA) is an ancient process, but has persisted throughout the evolution of most eukaryotes. This process has contributed to the mass of genomes of modern multicellular organisms,[18] at the same time keeping genomes in flux and presenting raw material for the de novo evolution of genes.[19]

3. Retroposition, not only segmental gene duplication, can also yield extra gene copies or smaller gene modules including regulatory elements for existing genes.[20][19][21]

Together with Stephen J. Gould, Brosius took the concept of exaptation to the genomic level.[22][23][24]

Encouraged by the stimulating findings surrounding BC1 RNA, in the mid-nineties he emphasized the significance of RNA coding genes in association with genome projects[25] and embarked on generating more cDNA libraries based on non-protein coding RNAs from mice and various model organisms, ringing in the era of RNomics,[26][27][28]

A number of small nucleolar RNAs prevalently expressed in the brain as well as imprinted (only expressed by one parental chromosome) were discovered in mice and men.[26][28]

Several of these mapped to the human Prader-Willi Syndrome locus, a neurodevelopmental disorder. After the individual deletion of all protein coding gene candidates of this locus in mouse models by others,[29] the Brosius laboratory deleted the cluster of Snord116 snoRNA genes and the corresponding non-protein coding exons of the host gene. They observed some of the same phenotypes as the human disorder, such as failure to thrive and short stature, but not obesity later in life or infertility.[30] This was confirmed by an independent study.[31]

Earlier, Brosius and coworkers demonstrated that mice lacking the BC1 RNA gene had deficiencies in exploratory behaviour in the laboratory and under semi-natural conditions.[32]

In addition to other RNomics discoveries, they were the first to demonstrate that certain tandem repeats were processed into CRISPR RNA units in Archaea.[33]

Brosius remains a long-time advocate[34] for the significance and wealth of RNA molecules even in modern cells. Yet, he is skeptical of the drastic transformation in the perception of RNA within the scientific community. The idea of pervasive importance of RNA was formerly frequently rejected. Currently, the trend of thought is to raise any background transcript or any detectable snippet of a transcript after processing or decay to a functional status.[35][36][37][38][39]

He observed analogous trends in the field of repetitive or transposed genomic elements (TEs) including retroposed elements.[20] These elements were initially considered to be junk, littering genomes, and proposed by only a few to constitute raw material for fortuitous and only occasional exaptations,[40] and to be responsible for the plasticity of genomes and the modular architecture of genes.[19][41][40] The current tide is moving in the opposite direction.[42] A plethora of functions have been assigned to TEs, one example being the bewildering spectrum of tasks allocated to the evolutionarily young primate-specific Alu elements. Such sweeping interpretations should be challenged.[43]

Other research areas include:

• de novo evolution of genes and parts thereof[44]
• the use of retroposon markers to establish phylogenetic relationships[45]
• the origin and evolution of life[46]
• evolutionary thought to address bioethical questions[47]
• RNA as diagnostic markers for various diseases including cancer[48]

• Associate Editor “PLoS Genetics” (2009- )
• Associate Editor “Journal of Molecular Evolution” (2004-2012)
• Editorial Board member "Scientific Reports" (2015- )
• Editorial Board member “PLoS ONE” (2010- )
• Editorial Board member “Mobile DNA” (2009- )
• Editorial Board member “Biology Direct” (2007- )
• Editorial Board member “RNA Biology” (2004- )
• Editorial Board member “RepBase Reports” (2001- )
• Editorial board member and European Editor "DNA and Cell Biology" (1986-2011)

• Institute of Experimental Pathology

• Brosius J NCBI Publication list