Journal
GENOME RESEARCH
Volume 29, Issue 9, Pages 1377-1388Publisher
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.247239.118
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Funding
- National Institutes of Health (NIH/NCATS) through the NIH Common Fund, Office of Strategic Coordination (OSC) [UH3TR00943-01]
- NCI [1R01 CA182905-01, 1R01CA222007-01A1]
- NIGMS [1R01GM122775-01]
- U54 grant [CA096297/CA096300-UPR/MDACC]
- Team DOD [CA160445P1]
- Chronic Lymphocytic Leukemia Moonshot Flagship project
- Sister Institution Network Fund (SINF) 2017 grant
- Estate of C.G. Johnson, Jr
- NIH NIGMS [RO1 GM103834, R35 GM126942]
- Swedish Research Council
- Swedish Cancer Society
- Swedish Childhood Cancer Foundation
- Crown Princess Margareta's Foundation for the Visually Impaired
- SINF StraCan
- King Gustaf V Jubilee Foundation
- Stockholm Cancer Society
- Stockholm County
- Karolinska Institute
- NIH/NCI [R01CA215753, R01CA219024]
- Pablove Foundation Accelerator Award
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The world of noncoding RNAs (ncRNAs) is composed of an enormous and growing number of transcripts, ranging in length from tens of bases to tens of kilobases, involved in all biological processes and altered in expression and/or function in many types of human disorders. The premise of this review is the concept that ncRNAs, like many large proteins, have a multidomain architecture that organizes them spatially and functionally. As ncRNAs are beginning to be imprecisely classified into functional families, we review here how their structural properties might inform their functions with focus on structural architecture-function relationships. We will describe the properties of interactor elements (IEs) involved in direct physical interaction with nucleic acids, proteins, or lipids and of structural elements (SEs) directing their wiring within the ncRNA interactor networks through the emergence of secondary and/or tertiary structures. We suggest that spectrums of letters (ncRNA elements) are assembled into words (ncRNA domains) that are further organized into phrases (complete ncRNA structures) with functional meaning (signaling output) through complex sentences (the ncRNA interactor networks). This semiotic analogy can guide the exploitation of ncRNAs as new therapeutic targets through the development of IE-blockers and/or SE-lockers that will change the interactor partners' spectrum of proteins, RNAs, DNAs, or lipids and consequently influence disease phenotypes.
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