Long non-coding RNAs: novel regulators of cellular physiology and function

Abstract

Long non-coding RNAs were once considered as “junk” RNA produced by aberrant DNA transcription. They are now understood to play central roles in diverse cellular processes from proliferation and migration to differentiation, senescence and DNA damage control. LncRNAs are classed as transcripts longer than 200 nucleotides that do not encode a peptide. They are relevant to many physiological and pathophysiological processes through their control of fundamental molecular functions. This review summarises the recent progress in lncRNA research and highlights the far-reaching physiological relevance of lncRNAs. The main areas of lncRNA research encompassing their characterisation, classification and mechanisms of action will be discussed. In particular, the regulation of gene expression and chromatin landscape through lncRNA control of proteins, DNA and other RNAs will be introduced. This will be exemplified with a selected number of lncRNAs that have been described in numerous physiological contexts and that should be largely representative of the tens-of-thousands of mammalian lncRNAs. To some extent, these lncRNAs have inspired the current thinking on the central dogmas of epigenetics, RNA and DNA mechanisms.

Angiotensin-(1–7) Analogue AVE0991 Modulates Astrocyte-Mediated Neuroinflammation via lncRNA SNHG14/miR-223-3p/NLRP3 Pathway and Offers Neuroprotection in a Transgenic Mouse Model of Alzheimer’s Disease

“…LncRNAs represent a subgroup of RNAs lacking protein-coding capacity. 39 Recently, lncRNAs were revealed to play an important role in modulating neuroinflammation and thus contributed to the pathogenesis of numerous neurological diseases including ischemic stroke, cerebral hemorrhage, epilepsy, Parkinson’s disease, and Alzheimer’s disease. 40–44 Based on this evidence, we then asked whether lncRNAs were involved in the AVE0991-induced inhibition of astrocytic NLRP3 inflammasome.…”

Network Approaches to Study Endogenous RNA Competition and Its Impact on Tissue-Specific microRNA Functions

“…This definition encompasses a highly heterogeneous group of transcripts regarding both biogenesis and functions. Among the latter, the regulation of gene expression by sponging miRNAs was first demonstrated in 2011 for linc-MD1 [ 44 ]. This lncRNA was found to act as decoy for two miRNAs, miR-133 and miR-135, controlling the timing of myoblast differentiation [ 44 ].…”

“…Among the latter, the regulation of gene expression by sponging miRNAs was first demonstrated in 2011 for linc-MD1 [ 44 ]. This lncRNA was found to act as decoy for two miRNAs, miR-133 and miR-135, controlling the timing of myoblast differentiation [ 44 ]. Around the same time as these discoveries, the universe of non-coding RNAs was being expanded by the identification of circular RNA molecules.…”

The endothelial-specific LINC00607 mediates endothelial angiogenic function

“…Recent studies suggest that long non-coding RNAs (lncRNAs) are essential in the regulation of cardiovascular gene programs [51, 59]. LncRNAs are RNA molecules longer than 200 nucleotides in length, which may lack apparent protein-coding potential.…”

“…LncRNAs are RNA molecules longer than 200 nucleotides in length, which may lack apparent protein-coding potential. They have independent functions as RNAs, separate from potential peptide coding abilities [51, 59]. Through different mechanisms lncRNAs impact on gene expression and therefore the cellular phenotype [59].…”