RNA, Genome Output and Input

Abstract

RNA, the transcriptional output of genomes, not only templates protein synthesis or directly engages in catalytic functions, but can feed back to the genome and serve as regulatory input for gene expression. Transcripts affecting the RNA abundance of other genes act by mechanisms similar to and in concert with protein factors that control transcription. Through recruitment or blocking of activating and silencing complexes to specific genomic loci, RNA and protein factors can favor transcription or lower the local gene expression potential. Most regulatory proteins enter nuclei from all directions to start the search for increased affinity to specific DNA sequences or to other proteins nearby genuine gene targets. In contrast, RNAs emerge from spatial point sources within nuclei, their encoding genes. A transcriptional burst can result in the local appearance of multiple nascent RNA copies at once, in turn increasing local nucleic acid density and RNA motif abundance before diffusion into the nuclear neighborhood. The confined initial localization of regulatory RNAs causing accumulation of protein co-factors raises the intriguing possibility that target specificity of non-coding, and probably coding, RNAs is achieved through gene/RNA positioning and spatial proximity to regulated genomic regions. Here we review examples of positional cis conservation of regulatory RNAs with respect to target genes, spatial proximity of enhancer RNAs to promoters through DNA looping and RNA-mediated formation of membrane-less structures to control chromatin structure and expression. We speculate that linear and spatial proximity between regulatory RNA-encoding genes and gene targets could possibly ease the evolutionary pressure on maintaining regulatory RNA sequence conservation.

Enhancer-Promoter Communication: It’s Not Just About Contact

“…Alternatively, contact-independent E-P communication has been proposed, a model in which information present at cis -regulatory regions is transferred to promoters even at a distance, for example by diffusion of post-translationally modified TFs at enhancers ( Karr et al, 2021 ). Enhancer RNAs or condensates may similarly facilitate transcriptional activation at a distance ( Morf et al, 2020 ). Although contact-independent E-P communication requires greater experimental validation, it offers a theoretical framework compatible with recent findings.…”

Identification of sheep lncRNAs related to the immune response to vaccines and aluminium adjuvants

“…Apart from a set of highly conserved and functionally characterised lncRNAs [35], lncRNAs show low sequence conservation. Hence, some may be functionless, function by the act of transcription itself [21,36,37], like the bidirectionally transcribed class of eRNAs [38], or have short functional elements that escape common conservation analyses. Some of the highly conserved lncRNAs identified in this work have been experimentally tested in humans.…”

The roles of lncRNA functions and regulatory mechanisms in the diagnosis and treatment of hepatocellular carcinoma

“…Most are nuclear, with some located in the cytoplasm. The involvement of lncRNAs in tumorigenesis, specifically, as they modulate both gene expression and signal transduction, is well documented (Carlevaro-Fita and Johnson, 2019; Maass Morf et al, 2020). Evidence suggests that LncRNAs have a role in every stage of HCC progression, from initial cell proliferation and differentiation through invasion, infiltration, and metastasis (Huo et al, 2017;Lim et al, 2019;Huang Z. et al, 2020).…”