Evolutionary Impact of the Noncoding Genome in Higher Organisms – Recent Insights Obtained from the Molecular and Cellular Level to Systems Biology

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Nuclei: Function, Transport and Receptors".

Deadline for manuscript submissions: 30 June 2024 | Viewed by 1553

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Department of Cardiology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, 12203 Berlin, Germany
Interests: cardiovascular diseases; immunopathogenesis; immunogenetics; molecular virology; noncoding human genome; nucleic acid-based therapeutics; RNA interference
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Special Issue Information

Dear Colleagues,

It is well known that 99% of the human genome does not encode proteins, but is transcriptionally active and gives rise to a broad spectrum of noncoding RNAs (ncRNAs) with complex regulatory and structural functions. The striking observation of a steeply increasing fraction of ncRNAs, in contrast to an only modest increase in the number of protein-coding genes, during evolution from simple organisms to humans, suggests an overwhelming role of ncRNAs arising from the noncoding genome in health and diseases. Importantly, however, ncRNAs can also be targets or tools of novel therapeutic strategies. Thus, RNA interference-mediating siRNAs are highly versatile novel ‘general purpose’ tools for the silencing of essentially any protein-coding or noncoding gene.

Research into the vast realm of the noncoding genome thus leads to fundamentally new therapeutic strategies based on a profoundly enhanced understanding of genome complexity. Beyond established knowledge in the field, this Special Issue aims to address remaining knowledge gaps and discuss newly emerging questions and concepts in research. We attempt to provide an up-to-date collection of the recent insights obtained by molecular and cellular biological methods, and progress reached by the application of systems biology approaches. Contributions will include work from neurosciences (brain research, neurological diseases, anthropology), immunology/genetics, and nucleic acid biochemistry, along with the intersections of these disciplines.

We look forward to colleagues illuminating unsolved questions: Have advanced immune systems incorporated evolutionary recent noncoding genomic regions to improve and balance their response to complex environmental  and endogenous challenges? Is noncoding genome evolution causally linked to brain evolution and may it explain critical differences between otherwise similar primate species? How many molecular players and levels of human genome complexity are still unknown to us? 

You may choose our Joint Special Issue in Non-Coding RNA.

Prof. Dr. Wolfgang Poller
Guest Editor

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Keywords

cell biology

immune cell functions

immunogenetics

noncoding genome

neurobiology

human evolution

brain evolution

brain-immune system interactions

nucleic acid-based therapeutics

RNA interference

Published Papers (1 paper)

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Review

35 pages, 8372 KiB  
Review
Exploration of the Noncoding Genome for Human-Specific Therapeutic Targets—Recent Insights at Molecular and Cellular Level
by Wolfgang Poller, Susmita Sahoo, Roger Hajjar, Ulf Landmesser and Anna M. Krichevsky
Cells 2023, 12(22), 2660; https://0-doi-org.brum.beds.ac.uk/10.3390/cells12222660 - 20 Nov 2023
Cited by 1 | Viewed by 1172
Abstract
While it is well known that 98–99% of the human genome does not encode proteins, but are nevertheless transcriptionally active and give rise to a broad spectrum of noncoding RNAs [ncRNAs] with complex regulatory and structural functions, specific functions have so far been [...] Read more.
While it is well known that 98–99% of the human genome does not encode proteins, but are nevertheless transcriptionally active and give rise to a broad spectrum of noncoding RNAs [ncRNAs] with complex regulatory and structural functions, specific functions have so far been assigned to only a tiny fraction of all known transcripts. On the other hand, the striking observation of an overwhelmingly growing fraction of ncRNAs, in contrast to an only modest increase in the number of protein-coding genes, during evolution from simple organisms to humans, strongly suggests critical but so far essentially unexplored roles of the noncoding genome for human health and disease pathogenesis. Research into the vast realm of the noncoding genome during the past decades thus lead to a profoundly enhanced appreciation of the multi-level complexity of the human genome. Here, we address a few of the many huge remaining knowledge gaps and consider some newly emerging questions and concepts of research. We attempt to provide an up-to-date assessment of recent insights obtained by molecular and cell biological methods, and by the application of systems biology approaches. Specifically, we discuss current data regarding two topics of high current interest: (1) By which mechanisms could evolutionary recent ncRNAs with critical regulatory functions in a broad spectrum of cell types (neural, immune, cardiovascular) constitute novel therapeutic targets in human diseases? (2) Since noncoding genome evolution is causally linked to brain evolution, and given the profound interactions between brain and immune system, could human-specific brain-expressed ncRNAs play a direct or indirect (immune-mediated) role in human diseases? Synergistic with remarkable recent progress regarding delivery, efficacy, and safety of nucleic acid-based therapies, the ongoing large-scale exploration of the noncoding genome for human-specific therapeutic targets is encouraging to proceed with the development and clinical evaluation of novel therapeutic pathways suggested by these research fields. Full article
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